自然早産の臨床的な特徴とそこから見えてきた治療戦略と限界、 そして、その予防策へと
早産は、自然早産と人工早産に分けられるが、およそ7割が自然早産とされている。また、この自然早産の既往歴自体が次回妊娠時の自然早産のリスクであるとされ、近年、その繰り返す確率は、22.3%であると報告されている。このような自然早産の原因は多岐に渡るが、子宮内の炎症(≒組織学的絨毛膜羊膜炎)がその中心である。よって、切迫早産と診断された際、性器出血、子宮口開大などの臨床症状から治療が行われるが、同時に直接評価が難しい子宮内環境(炎症と感染)がその予後に重要であると言える。特に、超早産などの早期の自然早産例では、羊水中の細菌とUreaplasma/Mycoplasmaの重複感染が関与していることがわ...
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| Published in | Reproductive Immunology and Biology Vol. 35; pp. 1 - 8 |
|---|---|
| Main Author | |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本生殖免疫学会
2020
|
| Subjects | |
| Online Access | Get full text |
| ISSN | 1881-607X 1881-7211 |
| DOI | 10.3192/jsirib.35.1 |
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| Abstract | 早産は、自然早産と人工早産に分けられるが、およそ7割が自然早産とされている。また、この自然早産の既往歴自体が次回妊娠時の自然早産のリスクであるとされ、近年、その繰り返す確率は、22.3%であると報告されている。このような自然早産の原因は多岐に渡るが、子宮内の炎症(≒組織学的絨毛膜羊膜炎)がその中心である。よって、切迫早産と診断された際、性器出血、子宮口開大などの臨床症状から治療が行われるが、同時に直接評価が難しい子宮内環境(炎症と感染)がその予後に重要であると言える。特に、超早産などの早期の自然早産例では、羊水中の細菌とUreaplasma/Mycoplasmaの重複感染が関与していることがわかってきた。このような病態を考慮し、抗菌薬の選択、黄体ホルモンを投与により、妊娠期間延長効果があることがわかったものの、すでに高度の炎症が存在するケースでは治療に難渋しやすく、治療限界があるとも言える。よって、妊娠中は子宮内環境が破綻しないような対策が必要である。妊娠維持に必須の制御性T細胞は、腸内Clostridium属と相関があることがマウスによる動物実験からわかってきた。また、腸内のClostridium属が少ない切迫早産患者は、早産しやすいことも分かっている。妊娠判明後、Clostridium属を含むプロバイオティクス療法が、自然早産を予防できる可能性があるのではなかろうか。 |
|---|---|
| AbstractList | 早産は、自然早産と人工早産に分けられるが、およそ7割が自然早産とされている。また、この自然早産の既往歴自体が次回妊娠時の自然早産のリスクであるとされ、近年、その繰り返す確率は、22.3%であると報告されている。このような自然早産の原因は多岐に渡るが、子宮内の炎症(≒組織学的絨毛膜羊膜炎)がその中心である。よって、切迫早産と診断された際、性器出血、子宮口開大などの臨床症状から治療が行われるが、同時に直接評価が難しい子宮内環境(炎症と感染)がその予後に重要であると言える。特に、超早産などの早期の自然早産例では、羊水中の細菌とUreaplasma/Mycoplasmaの重複感染が関与していることがわかってきた。このような病態を考慮し、抗菌薬の選択、黄体ホルモンを投与により、妊娠期間延長効果があることがわかったものの、すでに高度の炎症が存在するケースでは治療に難渋しやすく、治療限界があるとも言える。よって、妊娠中は子宮内環境が破綻しないような対策が必要である。妊娠維持に必須の制御性T細胞は、腸内Clostridium属と相関があることがマウスによる動物実験からわかってきた。また、腸内のClostridium属が少ない切迫早産患者は、早産しやすいことも分かっている。妊娠判明後、Clostridium属を含むプロバイオティクス療法が、自然早産を予防できる可能性があるのではなかろうか。 |
| Author | 米田, 哲 |
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| Copyright | 2020 日本生殖免疫学会 |
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| References | 20) Yoneda S. Method to evaluate intravenous maintenance tocolysis for preterm labor. J Obstet Gynaecol Res. In press 4) Yoneda S, Shiozaki A, Ito M, Yoneda N, Inada K, Yonezawa R, Kigawa M, Saito S. Accurate prediction of the stage of histological chorioamnionitis before delivery by amniotic fluid IL-8 level. Am J Reprod Immun 18) Ito M, Takamori A, Yoneda S, Shiozaki A, Tsuchida A, Matsumura K, Hamazaki K, Yoneda N, Origasa H, Inadera H, Saito S; 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. Environ Health Prev Med. 2019; 24(1): 25. 16) Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, Cheng G, Yamasaki S, Saito T, Ohba Y, Taniguchi T, Takeda K, Hori S, Ivanov II, Umesaki Y, Itoh K, Honda K. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011;331(6015): 337-41. 21) Yoneda S, Yoneda N, Fukuta K, Shima T, Nakashima A, Shiozaki A, Yoshino O, Kigawa M, Yoshida T and Saito S. In which preterm labor-patients is intravenous maintenance tocolysis effective? J Obstet Gynaecol Res. 2018; 44: 397-407. 1) Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008 Jan 5;371(9606):75-84. 7) Ueno T, Niimi H, Yoneda N, Yoneda S, Mori M, Tabata H, Minami H, Saito S, Kitajima I. Eukaryote-Made Thermostable DNA Polymerase Enables Rapid PCR-Based Detection of Mycoplasma, Ureaplasma and Other Bacteria in the Amniotic Fluid of Preterm Labor Cases. PLoS One. 2015;10(6):e0129032. 14) Yoneda S, Yoneda N, Shiozaki A, Yoshino O, Ueno T, Niimi H, Kitajima I, Tamura K, Kawasaki Y, Makimoto M, Yoshida T and Saito S. 17OHP-C in patients with spontaneous preterm labor and intact membranes: is there an effect according to the presence of intra-amniotic inflammation? Am J Reprod Immunol. 2018; 80: e12867. 5) Yoneda S, Sakai M, Sasaki Y, Shiozaki A, Hidaka T, Saito S. Interleukin-8 and glucose in amniotic fluid, fetal fibronectin in vaginal secretions and preterm labor index based on clinical variables are optimal predictive markers for preterm delivery in patients with intact membranes. J Obstet Gynaecol Res. 2007;33(1):38-44. 12) Yoneda S, Shiozaki A, Yoneda N, Ito M, Shima T, Fukuta K, Ueno T, Niimi H, Kitajima I, Kigawa M, Saito S. Antibiotic therapy increases the risk of preterm birth in preterm labor without intra-amniotic microbes, but may prolong the gestation period in preterm labor with microbes, evaluated by rapid and high sensitive PCR system. Am J Reprod Immunol. 2016; 75: 440-50. 13) Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003; 348(24): 2379-2385. 6) Yoneda S, Shiozaki A, Yoneda N, Shima T, Ito M, Yamanaka M, Hidaka T, Sumi S and Saito S. Prediction of exact delivery time in patients with preterm labor and intact membranes at admission by amniotic fluid interleukin-8 level and preterm labor index. J Obstet Gynecol Res. 37: 861-6, 2011. 15) Shiozaki A, Yoneda S, Yoneda N, Yonezawa R, Matsubayashi T, Seo G, Saito S. Intestinal microbiota is different in women with preterm birth: results from terminal restriction fragment length polymorphism analysis. PLoS One. 2014; 9(11): e111374. 19) Kirihara N, Kamitomo M, Tabira T, Hashimoto T, Taniguchi H, Maeda T. Effect of probiotics on perinatal outcome in patients at high risk of preterm birth. J Obstet Gynaecol Res. 2018; 44(2): 241-247. 17) Nordqvist M, Jacobsson B, Brantsæter AL, Myhre R, Nilsson S, Sengpiel V. Timing of probiotic milk consumption during pregnancy and effects on the incidence of preeclampsia and preterm delivery: a prospective observational cohort study in Norway. BMJ Open. 2018; 8(1): e018021. 8) Yoneda N, Yoneda S, Niimi H, Ueno T, Hayashi S, Ito M, Shiozaki A, Urushiyama D, Hata K, Suda W, Hattori M, Kigawa M, Kitajima I, Saito S. Polymicrobial amniotic fluid infection with Mycoplasma/Ureaplasma and other bacteria induces severe intra-amniotic inflammation associated with poor perinatal prognosis in preterm labor. Am J Reprod Immunol. 75; 112-25: 2016. 2) Seyama R, Makino S, Nojiri S, Takeda J, Suzuki T, Maruyama Y, Takeda S, Itakura A. Retrospective study of the recurrence risk of preterm birth in Japan. J Matern Fetal Neonatal Med. 2020 Feb 18:1-5. doi: .10.1080/14767058.2020.1727435 10) Yoneda N, Yoneda S, Niimi H, Ito M, Fukuta K, Ueno T, Ito M, Shiozaki A, Kigawa M, Kitajima I and Saito S. Sludge reflects intra-amniotic inflammation with or without microorganisms. Am J Reprod Immunol. 2018; 79: e12807. 11) Flenady V, Hawley G, Stock OM, Kenyon S, Badawi N.Prophylactic antibiotics for inhibiting preterm labour with intact membranes. Cochrane Database Syst Rev. 2013; (12): CD000246. 9) Romero R, Kusanovic JP, Espinoza J, Gotsch F, Nhan-Chang CL, Erez O, Kim CJ, Khalek N, Mittal P, Goncalves LF, Schaudinn C, Hassan SS, Costerton JW What is amniotic fluid 'sludge'? Ultrasound Obstet Gynecol. 2007 Oct;30(5):793-8. 3) Combs CA, Gravett M, Garite TJ, Hickok DE, Lapidus J, Porreco R, Rael J, Grove T, Morgan TK, Clewell W, Miller H, Luthy D, Pereira L, Nageotte M, Robilio PA, Fortunato S, Simhan H, Baxter JK, Amon E, Franco A, Trofatter K, Heyborne K; ProteoGenix/Obstetrix Collaborative Research Network. Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes. Am J Obstet Gynecol. 2014 Feb;210(2):125.e1-125.e15. doi: . Epub 2013 Nov 23.10.1016/j.ajog.2013.11.032 |
| References_xml | – reference: 4) Yoneda S, Shiozaki A, Ito M, Yoneda N, Inada K, Yonezawa R, Kigawa M, Saito S. Accurate prediction of the stage of histological chorioamnionitis before delivery by amniotic fluid IL-8 level. Am J Reprod Immun – reference: 20) Yoneda S. Method to evaluate intravenous maintenance tocolysis for preterm labor. J Obstet Gynaecol Res. In press – reference: 3) Combs CA, Gravett M, Garite TJ, Hickok DE, Lapidus J, Porreco R, Rael J, Grove T, Morgan TK, Clewell W, Miller H, Luthy D, Pereira L, Nageotte M, Robilio PA, Fortunato S, Simhan H, Baxter JK, Amon E, Franco A, Trofatter K, Heyborne K; ProteoGenix/Obstetrix Collaborative Research Network. Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes. Am J Obstet Gynecol. 2014 Feb;210(2):125.e1-125.e15. doi: . Epub 2013 Nov 23.10.1016/j.ajog.2013.11.032 – reference: 9) Romero R, Kusanovic JP, Espinoza J, Gotsch F, Nhan-Chang CL, Erez O, Kim CJ, Khalek N, Mittal P, Goncalves LF, Schaudinn C, Hassan SS, Costerton JW What is amniotic fluid 'sludge'? Ultrasound Obstet Gynecol. 2007 Oct;30(5):793-8. – reference: 18) Ito M, Takamori A, Yoneda S, Shiozaki A, Tsuchida A, Matsumura K, Hamazaki K, Yoneda N, Origasa H, Inadera H, Saito S; 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. Environ Health Prev Med. 2019; 24(1): 25. – reference: 21) Yoneda S, Yoneda N, Fukuta K, Shima T, Nakashima A, Shiozaki A, Yoshino O, Kigawa M, Yoshida T and Saito S. In which preterm labor-patients is intravenous maintenance tocolysis effective? J Obstet Gynaecol Res. 2018; 44: 397-407. – reference: 11) Flenady V, Hawley G, Stock OM, Kenyon S, Badawi N.Prophylactic antibiotics for inhibiting preterm labour with intact membranes. Cochrane Database Syst Rev. 2013; (12): CD000246. – reference: 1) Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008 Jan 5;371(9606):75-84. – reference: 2) Seyama R, Makino S, Nojiri S, Takeda J, Suzuki T, Maruyama Y, Takeda S, Itakura A. Retrospective study of the recurrence risk of preterm birth in Japan. J Matern Fetal Neonatal Med. 2020 Feb 18:1-5. doi: .10.1080/14767058.2020.1727435 – reference: 8) Yoneda N, Yoneda S, Niimi H, Ueno T, Hayashi S, Ito M, Shiozaki A, Urushiyama D, Hata K, Suda W, Hattori M, Kigawa M, Kitajima I, Saito S. Polymicrobial amniotic fluid infection with Mycoplasma/Ureaplasma and other bacteria induces severe intra-amniotic inflammation associated with poor perinatal prognosis in preterm labor. Am J Reprod Immunol. 75; 112-25: 2016. – reference: 14) Yoneda S, Yoneda N, Shiozaki A, Yoshino O, Ueno T, Niimi H, Kitajima I, Tamura K, Kawasaki Y, Makimoto M, Yoshida T and Saito S. 17OHP-C in patients with spontaneous preterm labor and intact membranes: is there an effect according to the presence of intra-amniotic inflammation? Am J Reprod Immunol. 2018; 80: e12867. – reference: 7) Ueno T, Niimi H, Yoneda N, Yoneda S, Mori M, Tabata H, Minami H, Saito S, Kitajima I. Eukaryote-Made Thermostable DNA Polymerase Enables Rapid PCR-Based Detection of Mycoplasma, Ureaplasma and Other Bacteria in the Amniotic Fluid of Preterm Labor Cases. PLoS One. 2015;10(6):e0129032. – reference: 16) Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, Cheng G, Yamasaki S, Saito T, Ohba Y, Taniguchi T, Takeda K, Hori S, Ivanov II, Umesaki Y, Itoh K, Honda K. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011;331(6015): 337-41. – reference: 12) Yoneda S, Shiozaki A, Yoneda N, Ito M, Shima T, Fukuta K, Ueno T, Niimi H, Kitajima I, Kigawa M, Saito S. Antibiotic therapy increases the risk of preterm birth in preterm labor without intra-amniotic microbes, but may prolong the gestation period in preterm labor with microbes, evaluated by rapid and high sensitive PCR system. Am J Reprod Immunol. 2016; 75: 440-50. – reference: 13) Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003; 348(24): 2379-2385. – reference: 17) Nordqvist M, Jacobsson B, Brantsæter AL, Myhre R, Nilsson S, Sengpiel V. Timing of probiotic milk consumption during pregnancy and effects on the incidence of preeclampsia and preterm delivery: a prospective observational cohort study in Norway. BMJ Open. 2018; 8(1): e018021. – reference: 10) Yoneda N, Yoneda S, Niimi H, Ito M, Fukuta K, Ueno T, Ito M, Shiozaki A, Kigawa M, Kitajima I and Saito S. Sludge reflects intra-amniotic inflammation with or without microorganisms. Am J Reprod Immunol. 2018; 79: e12807. – reference: 19) Kirihara N, Kamitomo M, Tabira T, Hashimoto T, Taniguchi H, Maeda T. Effect of probiotics on perinatal outcome in patients at high risk of preterm birth. J Obstet Gynaecol Res. 2018; 44(2): 241-247. – reference: 6) Yoneda S, Shiozaki A, Yoneda N, Shima T, Ito M, Yamanaka M, Hidaka T, Sumi S and Saito S. Prediction of exact delivery time in patients with preterm labor and intact membranes at admission by amniotic fluid interleukin-8 level and preterm labor index. J Obstet Gynecol Res. 37: 861-6, 2011. – reference: 15) Shiozaki A, Yoneda S, Yoneda N, Yonezawa R, Matsubayashi T, Seo G, Saito S. Intestinal microbiota is different in women with preterm birth: results from terminal restriction fragment length polymorphism analysis. PLoS One. 2014; 9(11): e111374. – reference: 5) Yoneda S, Sakai M, Sasaki Y, Shiozaki A, Hidaka T, Saito S. Interleukin-8 and glucose in amniotic fluid, fetal fibronectin in vaginal secretions and preterm labor index based on clinical variables are optimal predictive markers for preterm delivery in patients with intact membranes. J Obstet Gynaecol Res. 2007;33(1):38-44. |
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| Snippet | 早産は、自然早産と人工早産に分けられるが、およそ7割が自然早産とされている。また、この自然早産の既往歴自体が次回妊娠時の自然早産のリスクであるとされ、近年、その繰り... |
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| SubjectTerms | Ureaplasma/Mycoplasma プロバイオティクス 子宮内感染 子宮内炎症 自然早産 |
| Title | 自然早産の臨床的な特徴とそこから見えてきた治療戦略と限界、 そして、その予防策へと |
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