日本産科婦人科学会・日本産婦人科医会編：CQ302 切迫早産の診断と管理の注意点は？ 産婦人科診療ガイドライン―産科編2023, 146-150, 2023.
日本産科婦人科学会：切迫早産. 産科婦人科用語集・用語解説集 改訂第4版，金原出版，2018; 196.
日本産科婦人科学会・日本産婦人科医会編：CQ301 頸管無力症など、流早産ハイリスク妊婦の抽出とその対応は？ 産婦人科診療ガイドライン―産科編2023, 140-145, 2023.
日本産科婦人科学会：異常妊娠. 産婦人科研修の必修知識2011，2011; 200-205.
G S Berkowitz, E Papiernik
Epidemiology of preterm birth.
Epidemiol Rev. 1993;15(2):414-43.
Abstract/Text
日本産科婦人科学会・日本産婦人科医会編：CQ501 妊婦に子宮筋腫を認めた場合の対応は？ 産婦人科診療ガイドライン―産科編2023, 284-285, 2023.
日本産科婦人科学会・日本産婦人科医会編：CQ505 妊婦・授乳婦のう歯・歯周病に対する注意点は？ 産婦人科診療ガイドライン―産科編2023, 293-294, 2023.
日本産科婦人科学会編：妊娠中期・後期の異常. 1)切迫早産・早産. 産婦人科専門医のための必修知識2020年度版. B60～B63. 2020.
岡村均：研修医のための必修知識．C.産科疾患の診断・治療・管理 13．産科感染症の診断と治療,2002;N457-N463.
日本産科婦人科学会，日本産婦人科医会編：CQ303 前期破水の取り扱いは？ 産婦人科診療ガイドライン－産科編2014，2014;139-142.
日本医療機能評価機構編．第12回産科医療補償制度再発防止に関する報告書. 子宮内感染について（総括）. p26. 2022.
W J Morales
The effect of chorioamnionitis on the developmental outcome of preterm infants at one year.
Obstet Gynecol. 1987 Aug;70(2):183-6.
Abstract/Text
This report investigates the effect of chorioamnionitis on infant mental and psychomotor development at one year through the prospective study of 698 preterm pregnancies complicated by premature rupture of membranes and managed expectantly without antenatal corticosteroids or tocolytic agents. Ninety-two mothers (13%) developed chorioamnionitis, resulting in a statistically significant increase in neonatal mortality (25 versus 6%), respiratory distress syndrome (RDS) (62 versus 35%), intraventricular hemorrhage (56 versus 22%), and sepsis (28 versus 11%). A multidisciplinary team examined 43 surviving infants at corrected one year of life and measured their mental and psychomotor development by the Bayley scales. No statistically significant difference in outcomes was observed when their development was compared with that of a control group matched for birth weight, gestational age, severity of intraventricular hemorrhage, and severity of RDS.
研修医のための必修知識．D.産科疾患の診断・治療・管理 8．合併症妊娠の管理と治療,2008;N15-N19.
J D Iams, R L Goldenberg, P J Meis, B M Mercer, A Moawad, A Das, E Thom, D McNellis, R L Copper, F Johnson, J M Roberts
The length of the cervix and the risk of spontaneous premature delivery. National Institute of Child Health and Human Development Maternal Fetal Medicine Unit Network.
N Engl J Med. 1996 Feb 29;334(9):567-72. doi: 10.1056/NEJM199602293340904.
Abstract/Text
BACKGROUND: The role of the cervix in the pathogenesis of premature delivery is controversial. In a prospective, multicenter study of pregnant women, we used vaginal ultrasonography to measure the length of the cervix; we also documented the incidence of spontaneous delivery before 35 weeks' gestation.
METHODS: At 10 university-affiliated prenatal clinics, we performed vaginal ultrasonography at approximately 24 and 28 weeks of gestation in women with singleton pregnancies. We then assessed the relation between the length of the cervix and the risk of spontaneous preterm delivery.
RESULTS: We examined 2915 women at approximately 24 weeks of gestation and 2531 of these women again at approximately 28 weeks. Spontaneous preterm delivery (at less than 35 weeks) occurred in 126 of the women (4.3 percent) examined at 24 weeks. The length of the cervix was normally distributed at 24 and 28 weeks (mean [+/- SD], 35.2 +/- 8.3 mm and 33.7 +/- 8.5 mm, respectively). The relative risk of preterm delivery increased as the length of the cervix decreased. When women with shorter cervixes at 24 weeks were compared with women with values above the 75th percentile, the relative risks of preterm delivery among the women with shorter cervixes were as follows: 1.98 for cervical lengths at or below the 75th percentile (40 mm), 2.35 for lengths at or below the 50th percentile (35 mm), 3.79 for lengths at or below the 25th percentile (30 mm), 6.19 for lengths at or below the 10th percentile (26 mm), 9.49 for lengths at or below the 5th percentile (22 mm), and 13.99 for lengths at or below the 1st percentile (13 mm) (P < 0.001 for values at or below the 50th percentile; P = 0.008 for values at or below the 75th percentile). For the lengths measured at 28 weeks, the corresponding relative risks were 2.80, 3.52, 5.39, 9.57, 13.88, and 24.94 (P < 0.001 for values at or below the 50th percentile; P = 0.003 for values at the 75th percentile).
CONCLUSIONS: The risk of spontaneous preterm delivery is increased in women who are found to have a short cervix by vaginal ultrasonography during pregnancy.
H Leitich, C Egarter, A Kaider, M Hohlagschwandtner, P Berghammer, P Husslein
Cervicovaginal fetal fibronectin as a marker for preterm delivery: a meta-analysis.
Am J Obstet Gynecol. 1999 May;180(5):1169-76.
Abstract/Text
OBJECTIVE: We performed a meta-analysis to determine the value of cervicovaginal fetal fibronectin as a marker for preterm delivery.
STUDY DESIGN: Selection criteria confined the analysis to original, English-language reports of prospective studies including women at <37 weeks' gestation with intact amniotic membranes. For the outcomes of delivery at <37 or <34 weeks' gestation or delivery within 7, 14, 21, or 28 days after fibronectin sampling, we calculated sensitivity and specificity rates for each study, for subgroups of studies, and for all studies combined.
RESULTS: A total of 27 studies met our inclusion criteria. For the outcomes of delivery at <37 and <34 weeks' gestation, overall sensitivity rates were 56% and 61% and overall specificity rates were 84% and 83%, respectively. For the outcomes of delivery within 7, 14, 21, and 28 days, we calculated sensitivity rates of 76%, 68%, 61%, and 43% and specificity rates of 88%, 89%, 91%, and 93%, respectively. For the subgroup of patients with symptoms of preterm labor, sensitivity rates for delivery within 7, 14, 21, and 28 days of 89%, 78%, 76%, and 71% and specificity rates of 86%, 86%, 88%, and 83%, respectively, were calculated.
CONCLUSION: Among patients with symptoms of preterm labor, cervicovaginal fetal fibronectin appears to be among the most effective predictors of preterm delivery.
Austin Ugwumadu, Isaac Manyonda, Fiona Reid, Phillip Hay
Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: a randomised controlled trial.
Lancet. 2003 Mar 22;361(9362):983-8. doi: 10.1016/S0140-6736(03)12823-1.
Abstract/Text
BACKGROUND: Abnormal vaginal flora and bacterial vaginosis are associated with amplified risks of late miscarriage and spontaneous preterm delivery. We aimed to establish whether antibiotic treatment early in the second trimester might reduce these risks in a general obstetric population.
METHODS: We screened 6120 pregnant women attending hospital for their first antenatal visit--who were at 12-22 weeks' gestation (mean 15.6 weeks)--for bacterial vaginosis or abnormal vaginal flora. We used gram-stained slides of vaginal smears to diagnose abnormal vaginal flora or bacterial vaginosis, in accordance with Nugent's criteria. We randomly allocated 494 women with one of these signs to receive either clindamycin 300 mg or placebo orally twice daily for 5 days. Primary endpoints were spontaneous preterm delivery (birth > or =24 but <37 weeks) and late miscarriage (pregnancy loss > or =13 but <24 weeks). Analysis was intention to treat.
FINDINGS: Nine women were lost to follow-up or had elective termination. Thus, we analysed 485 women with complete outcome data. Women receiving clindamycin had significantly fewer miscarriages or preterm deliveries (13/244) than did those in the placebo group (38/241; percentage difference 10.4%, 95% CI 5.0-15.8, p=0.0003). Clindamycin also reduced adverse outcomes across the range of abnormal Nugent scores, with maximum effect in women with the highest Nugent score of 10.
INTERPRETATION: Treatment of asymptomatic abnormal vaginal flora and bacterial vaginosis with oral clindamycin early in the second trimester significantly reduces the rate of late miscarriage and spontaneous preterm birth in a general obstetric population.
S L Kenyon, D J Taylor, W Tarnow-Mordi, ORACLE Collaborative Group
Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial. ORACLE Collaborative Group.
Lancet. 2001 Mar 31;357(9261):989-94.
Abstract/Text
BACKGROUND: Preterm birth after spontaneous preterm labour is associated with death, neonatal disease, and long-term disability. Previous small trials of antibiotics for spontaneous preterm labour have reported inconclusive results. We did a randomised multicentre trial to resolve this issue.
METHODS: 6295 women in spontaneous preterm labour with intact membranes and without evidence of clinical infection were randomly assigned 250 mg erythromycin (n=1611), 325 mg co-amoxiclav (250 mg amoxicillin and 125 mg clavulanic acid; n=1550), both (n=1565), or placebo (n=1569) four times daily for 10 days or until delivery, whichever occurred earlier. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat.
FINDINGS: None of the trial antibiotics was associated with a lower rate of the composite primary outcome than placebo (erythromycin 90 [5.6%], co-amoxiclav 76 [5.0%], both antibiotics 91 [5.9%], vs placebo 78 [5.0%]). However, antibiotic prescription was associated with a lower occurrence of maternal infection.
INTERPRETATION: This trial provides evidence that antibiotics should not be routinely prescribed for women in spontaneous preterm labour without evidence of clinical infection.
ACOG Committee on Practice Bulletins--Obstetrics
ACOG practice bulletin. Management of preterm labor. Number 43, May 2003.
Int J Gynaecol Obstet. 2003 Jul;82(1):127-35.
Abstract/Text
Preterm birth is the leading cause of neonatal mortality in the United States, and preterm labor precedes 40-50% of preterm births. Preterm birth accounts for 35% of all U.S. health care spending for infants and 10% of all such spending for children. Approximately 467,000 live births annually (11.5% of all live births) occur before term in the United States, and preterm births are responsible for three quarters of neonatal mortality and one half of long-term neurologic impairments in children. The purpose of this document is to present the various methods proposed to manage preterm labor and the evidence for their roles in clinical practice. Despite the numerous management methods proposed the incidence of preterm birth has changed little over the past 40 years (Fig. 1). Uncertainty persists about the best strategies for managing preterm labor.
P N Tara, S Thornton
Current medical therapy in the prevention and treatment of preterm labour.
Semin Fetal Neonatal Med. 2004 Dec;9(6):481-9. doi: 10.1016/j.siny.2004.08.005.
Abstract/Text
The prevention of preterm birth should be one of the major aims of antenatal care. Unfortunately, identification of women who will subsequently deliver preterm is imprecise. Prevention is also difficult. Surgical prevention with cerclage may help a proportion of women. Medical prevention is currently limited to the identification and treatment of bacterial vaginosis, although recent studies have suggested that progesterone prophylaxis may be helpful in some women. Confirmation of efficacy and safety is required before progesterone is introduced as long-term prophylaxis for all women at high risk. The optimal medical treatment (rather than prevention) of threatened preterm labour is controversial. Tocolysis is generally accepted to improve neonatal outcome although this has never been convincingly demonstrated in appropriate trials. Antibiotics confer benefit in the presence of ruptured membranes but are not indicated in uncomplicated preterm labour. In future, it may be possible to identify a subgroup of women in preterm labour with intact membranes who will benefit from tocolysis. The choice of first-line tocolytic therapy is currently debated but atosiban or nifedipine are suggested in current UK guidelines. A direct comparison of these drugs is required in a clinical trial. Although indirect comparisons have been made, these are difficult to interpret due to methodological differences. Each of these drugs have their advocates. Nifedipine has been reported to delay delivery and improve outcome but there are inconsistencies in the clinical trials. Atosiban is also reported to delay delivery and is well tolerated but improved neonatal outcome may have been hidden in clinical trials due to the requirement for rescue tocolysis.
日本産科婦人科学会・日本産婦人科医会編：CQ601 妊娠中の細菌性腟症の取り扱いは？ 産婦人科診療ガイドライン―産科編2023, 298-299, 2023.
日本産科婦人科学会、日本本産婦人科医会：産婦人科診療ガイドライン―産科編2017,p335-337，2017.
Soromon Kataoka, Takashi Yamada, Kazutoshi Chou, Ryutaro Nishida, Mamoru Morikawa, Mashiho Minami, Hideto Yamada, Noriaki Sakuragi, Hisanori Minakami
Association between preterm birth and vaginal colonization by mycoplasmas in early pregnancy.
J Clin Microbiol. 2006 Jan;44(1):51-5. doi: 10.1128/JCM.44.1.51-55.2006.
Abstract/Text
To examine the association between colonization by two newly classified species of genital ureaplasmas (Ureaplasma parvum and U. urealyticum) in early pregnancy and subsequent late abortion or preterm birth at <34 weeks of gestation, four species of genital mycoplasmas--Mycoplasma genitalium, M. hominis, U. parvum, and U. urealyticum--as well as Chlamydia trachomatis and Neisseria gonorrhoeae were examined by PCR-based methods in a prospective cohort study of 877 women with singleton pregnancies at <11 weeks of gestation. Antibiotics were used only in cases in which C. trachomatis and/or N. gonorrhoeae was detected. Multivariate logistic-regression analysis was used to assess independent risk factors after taking maternal low body weight and past history of preterm birth into account. M. genitalium, M. hominis, U. parvum, U. urealyticum, C. trachomatis, and N. gonorrhoeae were detected in 0.8%, 11.2%, 52.0%, 8.7%, 3.2%, and 0.1% of these 877 women, respectively. Twenty-one (2.4%) women experienced late abortion or preterm birth at <34 weeks of gestation. Three factors-detection of U. parvum in the vagina (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.1 to 8.5); use of antibiotics, such as penicillin and cefatrizine, for incidental inflammatory complications before 22 weeks of gestation (OR, 4.2; 95% CI, 1.6 to 10.0); and past history of preterm birth (OR, 10.4; 95% CI, 2.7 to 40.5)-were independently associated with late abortion and preterm birth. In conclusion, vaginal colonization with U. parvum, but not U. urealyticum, is associated with late abortion or early preterm birth.
N Kanayama, L Chinarong, H Naruse, N Yamamoto, S Fujishiro, K Maehara, Y Morita, T Terao
[The effect of granulocyte elastase inhibitor (urinastatin) vaginal suppository on patients with imminent premature delivery].
Nihon Sanka Fujinka Gakkai Zasshi. 1992 Apr;44(4):477-82.
Abstract/Text
Cervical maturation, dilatation and uterine contraction in imminent premature delivery are closely related to chemical mediators from activated granulocytes which infiltrate into the cervix. It is known that urinastatin (urinary trypsin inhibitor, UTI) inhibits many kinds of chemical mediators from granulocytes and macrophages such as granulocyte elastase (elastase) and interleukin 1. We examined the effect of a UTI suppository on uterine contraction and the elastase level in cervical mucus in cases of imminent premature delivery. We treated 43 cases of imminent premature delivery with tocolysis index 3 or 4 with 4 kinds of therapy: Group A (N = 12): ritodorine drop infusion therapy; Group B (N = 9): daily UTI suppository (1,000U) therapy; Group C (N = 14): daily UTI suppository + ritodorine drop infusion therapy; Group D: daily UTI suppository + ritodorine drop infusion + antibiotics (oral cepharosporine) therapy. The elastase level of cervical mucus before treatment was 0.76 +/- 0.40 micrograms/ml in group A, 0.93 +/- 0.43 micrograms/ml in group B, 0.85 +/- 0.40 micrograms/ml in group C and 0.90 +/- 0.41 micrograms/ml in group D. There was no significant difference between these groups. The elastase level in cervical mucus was 0.75 +/- 0.47 micrograms/ml in group A, 0.27 +/- 0.35 micrograms/ml in group B, 0.27 +/- 0.33 micrograms/ml in group C and 0.30 +/- 0.19 micrograms/ml in group D, respectively. The elastase level was decreased significantly in groups B, C and D. The time taken to depress uterine contraction was 65 +/- 66 min in group A, 375 +/- 336 min in group B, 70 +/- 64 min in group C and 58 +/- 53 min in group D, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Kikkawa M, Matsubara S, Takatoku M, et al.: Granulocyte colony stimulating factor for the treatment of ritodrine induced neutropenia. J Obstet Gynaecol Res 2008; 34: 286―290.
H Minakami, T Takahashi, A Izumi, H Itoi, T Tamada
Enlargement of the salivary gland after ritodrine treatment in pregnant women.
BMJ. 1992 Jun 27;304(6843):1668.
Abstract/Text
Dwight J Rouse, Deborah G Hirtz, Elizabeth Thom, Michael W Varner, Catherine Y Spong, Brian M Mercer, Jay D Iams, Ronald J Wapner, Yoram Sorokin, James M Alexander, Margaret Harper, John M Thorp, Susan M Ramin, Fergal D Malone, Marshall Carpenter, Menachem Miodovnik, Atef Moawad, Mary J O'Sullivan, Alan M Peaceman, Gary D V Hankins, Oded Langer, Steve N Caritis, James M Roberts, Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network
A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy.
N Engl J Med. 2008 Aug 28;359(9):895-905. doi: 10.1056/NEJMoa0801187.
Abstract/Text
BACKGROUND: Research suggests that fetal exposure to magnesium sulfate before preterm birth might reduce the risk of cerebral palsy.
METHODS: In this multicenter, placebo-controlled, double-blind trial, we randomly assigned women at imminent risk for delivery between 24 and 31 weeks of gestation to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour, or matching placebo. The primary outcome was the composite of stillbirth or infant death by 1 year of corrected age or moderate or severe cerebral palsy at or beyond 2 years of corrected age.
RESULTS: A total of 2241 women underwent randomization. The baseline characteristics were similar in the two groups. Follow-up was achieved for 95.6% of the children. The rate of the primary outcome was not significantly different in the magnesium sulfate group and the placebo group (11.3% and 11.7%, respectively; relative risk, 0.97; 95% confidence interval [CI], 0.77 to 1.23). However, in a prespecified secondary analysis, moderate or severe cerebral palsy occurred significantly less frequently in the magnesium sulfate group (1.9% vs. 3.5%; relative risk, 0.55; 95% CI, 0.32 to 0.95). The risk of death did not differ significantly between the groups (9.5% vs. 8.5%; relative risk, 1.12; 95% CI, 0.85 to 1.47). No woman had a life-threatening event.
CONCLUSIONS: Fetal exposure to magnesium sulfate before anticipated early preterm delivery did not reduce the combined risk of moderate or severe cerebral palsy or death, although the rate of cerebral palsy was reduced among survivors. (ClinicalTrials.gov number, NCT00014989.)
2008 Massachusetts Medical Society
D Roberts, S Dalziel
Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.
Cochrane Database Syst Rev. 2006 Jul 19;(3):CD004454. doi: 10.1002/14651858.CD004454.pub2. Epub 2006 Jul 19.
Abstract/Text
BACKGROUND: Respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and disability.
OBJECTIVES: To assess the effects on fetal and neonatal morbidity and mortality, on maternal mortality and morbidity, and on the child in later life of administering corticosteroids to the mother before anticipated preterm birth.
SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (30 October 2005).
SELECTION CRITERIA: Randomised controlled comparisons of antenatal corticosteroid administration (betamethasone, dexamethasone, or hydrocortisone) with placebo or with no treatment given to women with a singleton or multiple pregnancy, expected to deliver preterm as a result of either spontaneous preterm labour, preterm prelabour rupture of the membranes or elective preterm delivery.
DATA COLLECTION AND ANALYSIS: Two review authors assessed trial quality and extracted data independently.
MAIN RESULTS: Twenty-one studies (3885 women and 4269 infants) are included. Treatment with antenatal corticosteroids does not increase risk to the mother of death, chorioamnionitis or puerperal sepsis. Treatment with antenatal corticosteroids is associated with an overall reduction in neonatal death (relative risk (RR) 0.69, 95% confidence interval (CI) 0.58 to 0.81, 18 studies, 3956 infants), RDS (RR 0.66, 95% CI 0.59 to 0.73, 21 studies, 4038 infants), cerebroventricular haemorrhage (RR 0.54, 95% CI 0.43 to 0.69, 13 studies, 2872 infants), necrotising enterocolitis (RR 0.46, 95% CI 0.29 to 0.74, eight studies, 1675 infants), respiratory support, intensive care admissions (RR 0.80, 95% CI 0.65 to 0.99, two studies, 277 infants) and systemic infections in the first 48 hours of life (RR 0.56, 95% CI 0.38 to 0.85, five studies, 1319 infants). Antenatal corticosteroid use is effective in women with premature rupture of membranes and pregnancy related hypertension syndromes.
AUTHORS' CONCLUSIONS: The evidence from this new review supports the continued use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. A single course of antenatal corticosteroids should be considered routine for preterm delivery with few exceptions. Further information is required concerning optimal dose to delivery interval, optimal corticosteroid to use, effects in multiple pregnancies, and to confirm the long-term effects into adulthood.
Anthony C Sciscione
Maternal activity restriction and the prevention of preterm birth.
Am J Obstet Gynecol. 2010 Mar;202(3):232.e1-5. doi: 10.1016/j.ajog.2009.07.005. Epub 2009 Sep 20.
Abstract/Text
Activity restriction is 1 of the most common interventions used in obstetrics. Although it is used for many reasons, 1 of the most common is to prevent preterm birth in those at risk. This review of the literature describes the potential advantages, disadvantages, and efficacy of activity restriction for the prevention of preterm birth.
Copyright 2010 Mosby, Inc. All rights reserved.
Baumgarten K, Gruber W. ：Tocolyseindex. In: Dudenhausen JW, Saling E, eds. Perinatale Medizin. Stuttgart: Georg Thieme Verlag, 1974; 197-199.
