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Oxytocin receptor antagonists for inhibiting preterm labour

  1. Vicki Flenady1,*,
  2. Hanna E Reinebrant1,
  3. Helen G Liley2,
  4. Eashan G Tambimuttu3,
  5. Dimitri NM Papatsonis4

Editorial Group: Cochrane Pregnancy and Childbirth Group

Published Online: 6 JUN 2014

Assessed as up-to-date: 1 DEC 2013

DOI: 10.1002/14651858.CD004452.pub3


How to Cite

Flenady V, Reinebrant HE, Liley HG, Tambimuttu EG, Papatsonis DNM. Oxytocin receptor antagonists for inhibiting preterm labour. Cochrane Database of Systematic Reviews 2014, Issue 6. Art. No.: CD004452. DOI: 10.1002/14651858.CD004452.pub3.

Author Information

  1. 1

    Mater Research Institute - The University of Queensland (MRI-UQ), Translating Research Into Practice (TRIP) Centre, Brisbane, Queensland, Australia

  2. 2

    Mater Mothers’ Hospital, Mater Research, The University of Queensland, South Brisbane, Australia

  3. 3

    Royal Brisbane and Women's Hospital, Department of Gynaecology Oncology/Obstetrics and Gynaecology, Brisbane, Queensland, Australia

  4. 4

    Amphia Hospital Breda, Department of Obstetrics and Gynaecology, Breda, Netherlands

*Vicki Flenady, Translating Research Into Practice (TRIP) Centre, Mater Research Institute - The University of Queensland (MRI-UQ), Level 2 Aubigny Place, Mater Health Services, Annerley Road, Woolloongabba, Brisbane, Queensland, 4102, Australia. vflenady@mmri.mater.org.au.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 6 JUN 2014

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References

References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
  6. References to other published versions of this review
Cabar 2008 {published data only}
  • Cabar FR, Bittar RE, Gomes CM, Zugab M. Atosiban as a tocolytic agent: a new proposal of a therapeutic approach. Revista Brasileira de Ginecologia y Obstetricia 2008;30(2):87-92.
European 2001 {published data only}
  • The European Atosiban Study Group. The oxytocin antagonist atosiban versus the ß-agonist terbutaline in the treatment of preterm labor: a randomized, double-blind, controlled study. Acta Obstetricia et Gynecologica Scandinavica 2001;80:413-22.
  • The Worldwide Atosiban versus Beta-antagonists Study Group. Effectiveness and safety of the oxytocin antagonist atosiban versus beta-adrenergic agonists in the treatment of preterm labour. BJOG 2001;108:133-42.
French/Australian 2001 {published data only}
  • French/Australian Atosiban Investigators Group. Treatment of preterm labor with the oxytocin antagonist atosiban: a double-blind, randomized, controlled comparison with salbutamol. European Journal Obstetrics, Gynecology and Reproductive Biology 2001;98:177-85.
  • The Worldwide Atosiban versus Beta-antagonists Study Group. Effectiveness and safety of the oxytocin antagonist atosiban versus beta-adrenergic agonists in the treatment of preterm labour. BJOG 2001;108:133-42.
Goodwin 1994 {published data only}
  • Goodwin TM, Paul R, Silver H, Spellacy W, Parsons M, Chez R, et al. The effect of the oxytocin antagonist atosiban on preterm uterine activity in the human. American Journal of Obstetrics and Gynecology 1994;170:474-8.
  • Goodwin TM, Paul RH, Silver H, Parsons M, Chez R, Spellacy W, et al. Safety and efficacy of the oxytocin antagonist atosiban in threatened preterm labor: initial US trial. American Journal of Obstetrics and Gynecology 1992;166:359.
Goodwin 1996 {published data only}
  • Goodwin TM, Valenzuela G, Silver H, Hayashi R, Creasy GW, Lane R. Treatment of preterm labor with the oxytocin antagonist atosiban. American Journal of Perinatology 1996;13(3):143-6.
  • Goodwin TM, Valenzuela GJ, Silver H, Creasy G, Atosiban Study Group. Dose ranging study of the oxytocin antagonist atosiban in the treatment of preterm labor. Obstetrics & Gynecology 1996;88(3):331-6.
Kashanian 2005 {published data only}
  • Kashanian M, Akbarian AR, Soltanzadeh M. Atosiban and nifedipin for the treatment of preterm labor. International Journal of Gynecology & Obstetrics 2005;91(1):10-4.
  • Kashanian M, Soltanzadeh M, Sheikh Ansari N. Atosiban and nifedipin for the treatment of preterm labor. BJOG: an international journal of obstetrics and gynaecology 2008;115(s1):69.
Lin 2009 {published data only}
  • Lin CH, Lin SY, Shyu MK, Chen SU, Lee CN. Randomized trial of oxytocin antagonist atosiban versus beta-adrenergic agonists  in the treatment of spontaneous preterm labor in Taiwanese women. Journal of the Formosan Medical Association = Taiwan Yi Zhi 2009;108(6):493-501.
Moutquin 2000 {published data only}
  • Moutquin J, Rabinovici J. Comparison of atosiban versus ritodrine in the treatment of pre-term labour. Acta Obstetrica et Gynecologica Scandinavica 1997;76(167):33.
  • Moutquin JM, Sherman D, Cohen H, Mohide PT, Hochner-Celnikier D, Fejgin M, et al. Double-blind, randomized, controlled trial of atosiban and ritodrine in the treatment of preterm labor: a multicenter effectiveness and safety study. American Journal of Obstetrics and Gynecology 2000;182(5):1191-9.
Nonnenmacher 2009 {published data only}
  • Nonnenmacher A, Hopp H, Dudenhausen J. Effectiveness and safety of atosiban vs. pulsatile administration of fenoterol in the treatment of preterm labour. Zeitschrift fur Geburtshilfe und Neonatologie 2009;213(5):201-6.
Richter 2005 {published data only}
  • Richter ON, Dorn C, van de Vondel P, Ulrich U, Schmolling J. Tocolysis with atosiban: experience in the management of premature labor before 24 weeks of pregnancy. Archives of Gynecology and Obstetrics 2005;272(1):26-30.
Romero 2000 {published data only}
  • Goodwin TM. 1st International preterm labour congress. Strategies to prevent the morbidity and mortality associated with prematurity; 2002 June 27-30. Le Montreux Palace, Montreux Switzerland. 2002.
  • Goodwin TM. Long-term safety with oxytocin antagonists. 4th World Congress on Controversies in Obstetrics, Gynecology and Infertility; 2003 April 24-27; Berlin, Germany. 2003:291.
  • Goodwin TM, Randall H, Perry K, Menard MK, Bauer C, Shangold G, et al. A report on infant outcomes at 6 and 12 months after the use of atosiban in the management of preterm labor. 46th ACOG Annual Meeting; 1998 May 9-13; New Orleans, Louisiana. 1998.
  • Goodwin TM, Randall H, Perry K, Menard MK, Bauer C, Shangold G, et al. A report on infant outcomes up to 24 months after the use of atosiban in the management of preterm labor. 46th ACOG Annual Meeting; 1998 May 9-13; New Orleans, Louisiana. 1998.
  • Romero R, Sibai BM, Sanchez-Ramos L, Valenzuela GJ, Veille JC, Tabor B, et al. An oxytocin receptor antagonist (atosiban) in the treatment of preterm labor: a randomized, double-blind, placebo-controlled trial with tocolytic rescue. American Journal of Obstetrics and Gynecology 2000;182(5):1173-83.
  • Sibai B, Romero R, Sanchex-Ramos L, Valenzuela G, Veille J, Tabor B, et al. A double-blind placebo-controlled trial of an oxytocin-receptor antagonist (antocin) in the treatment of preterm labor. American Journal of Obstetrics and Gynecology 1997;176(1 Pt 2):S2.
  • Silver H, Valenzuela G, Sanchez-Ramos L, Romero R, Sibai B, Goodwin T, et al. Maternal side effects and safety of the oxytocin receptor antagonist antocin. American Journal of Obstetrics and Gynecology 1997;176(1 Pt 2):S45.
Salim 2012 {published data only}
  • Garmi G. Nifedipine compared to atosiban for treating preterm labor [ClinicalTrials.gov (http://clinicaltrials.gov/)]. accessed 9 April 2008.
  • Salim R, Garmi G, Nachum Z, Zafran N, Baram S, Shalev E. Nifedipine compared with atosiban for treating preterm labor: A randomized controlled trial. Obstetrics and Gynecology 2012;120(6):1323-31.
Shim 2006 {published data only}
Thornton 2009 {published data only}
  • Arce JC. A proof of concept study assessing the effect of four different stage bolus intravenous doses of FE200440 and placebo on stopping preterm labor (ongoing trial). ClinicalTrials.gov (http://clinicaltrials.gov/) (accessed 21 March 2006).
  • Thornton S, Goodwin TM, Greisen G, Hedegaard M, Arce JC. The effect of a selective oxytocin antagonist (barusiban) in threatened preterm labour: a randomized, double-blind, placebo-controlled trial. 55th Annual Meeting of the Society of Gynecologic Investigation; 2008 March 26-29; San Diego, USA. 2008:Abstract no: 129.
  • Thornton S, Goodwin TM, Greisen G, Hedegaard M, Arce JC. The effect of barusiban on plasma concentrations and uterine contractility in threatened preterm labour: a randomised, double-blind, placebo-controlled trial. Archives of Disease in Childhood. Fetal and Neonatal Edition 2008;93(Suppl 1):Fa11-Fa12.
  • Thornton S, Goodwin TM, Greisen G, Hedegaard M, Arce JC. The effect of barusiban, a selective oxytocin antagonist, in threatened preterm labor at late gestational age: a randomized, double-blind, placebo-controlled trial. American Journal of Obstetrics and Gynecology 2009;200(6):627.e1-627.e10.

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
  6. References to other published versions of this review
Al-Omari 2006 {published data only}
  • Al-Omari WR, Al-Shammaa HB, Al-Tikriti EM, Ahmed KW. Atosiban and nifedipine in acute tocolysis: a comparative study. European Journal of Obstetrics & Gynecology and Reproductive Biology 2006;128(1-2):129-34.
  • Al-Omari WR, Al-Tikri E, Al-Shammaa H. Atosiban and nifedipine in acute tocolysis, comparative study. XVIIIth European Congress of Obstetrics and Gynaecology; May 12-15; Athens, Greece. 2004:103.
de Heus 2008 {published data only}
  • de Heus R, Mulder EJ, Derks JB, Korver PH, van Wolfswinkel L, Visser GH. A prospective randomized trial of acute tocolysis in term labour with atosiban or ritodrine. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2008;139(2):139-45.
Gagnon 1998 {published data only}
  • Gagnon D, Martens L, Creasy G, Henke C. An economic analysis of atosiban maintenance therapy in preterm labor. American Journal of Obstetrics and Gynecology 1998;178(1 Pt 2):S181.
Husslein 2006 {published data only}
  • Anonymous. TREASURE (Tractocile efficacy assessment survey in Europe). Trial to commence in July. http://www.ferring.com/ (accessed 24 May 2004).
  • Husslein P, Roura LC, Dudenhausen J, Helmer H, Frydman R, Rizzo N, et al. Clinical practice evaluation of atosiban in preterm labour management in six European countries. BJOG: an international journal of obstetrics and gynaecology 2006;113(Suppl 3):105-10.
Husslein 2007 {published data only}
  • Husslein P, Cabero Roura L, Dudenhausen JW, Helmer H, Frydman R, Rizzo N, et al. Atosiban versus usual care for the management of preterm labor. Journal of Perinatal Medicine 2007;35(4):305-13.
Poppiti 2009 {published data only}
  • Poppiti R, Nazzaro G, De Placido G, Palmieri T, Locci M. Prevention of preterm delivery in twin pregnancies with atosiban. Journal of Maternal-Fetal & Neonatal Medicine 2009;22(Suppl 1):61.
Steinwall 2005 {published data only}
  • Steinwall M, Bossmar T, Brouard R, Laudanski T, Olofsson P, Urban R, et al. The effect of relcovaptan (SR 49059), an orally active vasopressin V1a receptor antagonist, on uterine contractions in preterm labor. Gynecological Endocrinology 2005;20(2):104-5.
Valenzuela 1997 {published data only}
  • Valenzuela G, Diaz A, Germain A, Foster T, Hayashi R, Seron-Ferre M. Estradiol levels are increased before and after preterm labor treatment with an oxytocin (OT) antagonist: evidence for chronic activation of the mechanism of labor. Acta Obstetricia et Gynecologica Scandinavica 1997;76(167):88.
Valenzuela 2000 {published data only}
  • Sanchez-Ramos L, Valenzuela G, Romero R, Silver H, Koltun W, Millar L, et al. A double-blind placebo-controlled trial of oxytocin receptor antagonist (antocin) maintenance therapy in patients with preterm labor. American Journal of Obstetrics and Gynecology 1997;176(1 Pt 2):S30.
  • Valenzuela GJ, Sanchez-Ramos L, Romero R, Silver HM, Koltun WD, Millar L, et al. Maintenance treatment of preterm labor with the oxytocin antagonist atosiban. The atosiban ptl-098 study group. American Journal of Obstetrics and Gynecology 2000;182(5):1184-90.

References to studies awaiting assessment

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
  6. References to other published versions of this review
de Heus 2009 {published data only}
  • de Heus R, Mulder EJ, Derks JB, Visser GH. The effects of the tocolytics atosiban and nifedipine on fetal movements, heart rate and blood flow. Journal of Maternal-Fetal & Neonatal Medicine 2009;22(6):485-90.
Lenzen 2012 {published data only}
  • Lenzen V, Bartz C, Rath WH. Atosiban versus fenoterol treatment of pre-term labour: randomised, prospective, multicentre study [Atosiban versus fenoterol zur behandlung vorzeitiger wehen: randomisierte, prospektive multizenterstudie]. Archives of Gynecology and Obstetrics 2012;286(Suppl 1):S197-S198.
Neri 2009 {published data only}
  • Neri I, Monari F, Valensise H, Facchinetti F, Bellafronte M, Volpe A. Computerized evaluation of fetal heart rate during tocolytic treatment: comparison between atosiban and ritodrine. Journal of Maternal-Fetal and Neonatal Medicine 2008;21(Suppl 1):22.
  • Neri I, Monari F, Valensise H, Vasapollo B, Facchinetti F, Volpe A. Computerized evaluation of fetal heart rate during tocolytic treatment: comparison between atosiban and ritodrine. American Journal of Perinatology 2009;26(4):259-63.
Renzo 2003 {published data only}
  • Renzo DGC, Mignosa MM, Rosati A, Burnelli L, Epicoco G, Luzi G. Can we effectively arrest premature labour in women with multiple gestations or other high-risk factors?. 4th World Congress on Controversies in Obstetrics, Gynecology & Infertility; 2003 April 24-27; Berlin, Germany. 2003:286-90.
Snidow 2013 {published data only}
  • Anonymous. The safety, tolerability and metabolism of GSK221149A, in pregnant women (34-36 weeks), in preterm labor. ClinicalTrials.gov (http://clinicaltrials.gov/) (accessed 21 June 2007).
  • Snidow J, Miller H, Valenzuela G, Thornton S, Stier B, Clayton L, et al. A multicenter, randomized, double-blind, placebo-controlled phase 2 trial of retosiban, a selective oxytocin receptor antagonist, for the management of preterm labor. American Journal of Obstetrics and Gynecology 2013;208(1 Suppl 1):S155.

References to ongoing studies

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
  6. References to other published versions of this review
APOSTEL III {published data only}
  • Heida K. Nifedipine versus Atosiban in the treatment of threatened preterm labour: APOSTEL III. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2947 (accessed 6 January 2014).

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
  6. References to other published versions of this review
Akerlund 1999
  • Akerlund M, Bossmar T, Brouard R, Kostrzewska A, Laudanski T, Lemancewicz A, et al. Receptor binding of oxytocin and vasopressin antagonists and inhibitory effects on isolated myometrium from preterm and term pregnant women. British Journal of Obstetrics and Gynaecology 1999;106(10):1047-53.
Anotayanonth 2006
  • Anotayanonth S, Subhedar NV, Neilson JP, Harigopal S. Betamimetics for inhibiting preterm labour. Cochrane Database of Systematic Reviews 2006, Issue 4. [DOI: 10.1002/14651858.CD004352.pub2]
Blencowe 2012
  • Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 2012 Jun 9;379(9832):2162-72.
Borthwick 2013
  • Borthwick AD, Liddle J. Retosiban and epelsiban: potent and selective orally available oxytocin antagonists. In: Dömling A editor(s). Protein-Protein Interactions in Drug Discovery. KGaA, Weinheim, Germany: Wiley-VCH Verlag GmbH & Co, 2013:225-56.
Chang 2013
  • Chang HH, Larson J, Blencowe H, Spong CY, Howson CP, Cairns-Smith S, et al. Preventing preterm births: analysis of trends and potential reductions with interventions in 39 countries with very high human development index. Lancet 2013;381(9862):223-34.
Coomarasamy 2003
Crowley 1996
Crowther 2002
  • Crowther CA, Hiller JE, Doyle LW. Magnesium sulphate for preventing preterm birth in threatened preterm labour. Cochrane Database of Systematic Reviews 2002, Issue 4. [DOI: 10.1002/14651858.CD001060]
Dorling 2008
Doyle 2009
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Duckitt 2002
  • Duckitt K, Thornton S. Nitric oxide donors for the treatment of preterm labour. Cochrane Database of Systematic Reviews 2002, Issue 3. [DOI: 10.1002/14651858.CD002860]
FDA 1998a
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FDA 1998b
  • Advisory Committee for Reproductive Health Drugs. Issue-NDA 20-797 Antocin, (atosiban injection) for use in the management of preterm labor. Centre for Drug Evaluation and Research, Food and Drug Administration. Gaithersburg, Maryland April 20 1998:81.
FDA 2011
  • U.S. Food, Drug Administration. Drug Safety Communication: New warnings against use of terbutaline to treat preterm labor. http://www.fda.gov/Drugs/DrugSafety/ucm243539.htm.
Gates 2004
Goldenberg 2008
Goodwin 1996b
Goodwin 1998a
  • Goodwin TM, Randall H, Perry K, Menard MK, Bauer C, Shangold G, et al. A report on infant outcomes up to 24 months of age after the use of atosiban in the management of preterm labour. 46th ACOG annual meeting; 1998 May 9-13; New Orleans, Louisiana. 1998.
Goodwin 1998b
Gyetvai 1999
Haas 2012
Higgins 2002
Higgins 2011
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Khanprakob 2012
King 1988
King 2003
  • King JF, Flenady VJ, Papatsonis DNM, Dekker GA, Carbonne B. Calcium channel blockers for inhibiting preterm labour. Cochrane Database of Systematic Reviews 2003, Issue 1. [DOI: 10.1002/14651858.CD002255]
King 2005
Koks 1998
  • Koks CA, Brolmann HA, de Kleine MJ, Manger PA. A randomized comparison of nifedipine and ritodrine for suppression of preterm labor. European Journal of Obstetrics & Gynecology and Reproductive Biology 1998;77(2):171-6.
Lasswell 2010
  • Lasswell SM, Barfield WD, Rochat RW, Blackmon L. Perinatal regionalization for very low-birth-weight and very preterm infants: a meta-analysis. JAMA 2013;304(9):992-1000.
Liu 2012
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Melin 1994
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Papatsonis 2004
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Petrou 2011
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Plunkett 2008
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Roberts 2006
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WHO 2012
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Yelland 2011
Zeitlin 2008
  • Zeitlin J, Draper ES, Kollée L, Milligan D, Boerch K, Agostino R, et al. for the MOSAIC research group. Differences in rates and short-term outcome of live births before 32 weeks of gestation in Europe in 2003: results from the MOSAIC cohort. Pediatrics 2008;121(4):e936-e944.

References to other published versions of this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
  6. References to other published versions of this review
Papatsonis 2005