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Maintenance therapy with oxytocin antagonists for inhibiting preterm birth after threatened preterm labour

  1. Dimitri NM Papatsonis1,*,
  2. Vicki Flenady2,
  3. Helen G Liley3

Editorial Group: Cochrane Pregnancy and Childbirth Group

Published Online: 13 OCT 2013

Assessed as up-to-date: 28 AUG 2013

DOI: 10.1002/14651858.CD005938.pub3


How to Cite

Papatsonis DNM, Flenady V, Liley HG. Maintenance therapy with oxytocin antagonists for inhibiting preterm birth after threatened preterm labour. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD005938. DOI: 10.1002/14651858.CD005938.pub3.

Author Information

  1. 1

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

  2. 2

    Mater Health Services, Translating Research Into Practice (TRIP) Centre - Mater Research, Woolloongabba, Queensland, Australia

  3. 3

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

*Dimitri NM Papatsonis, Department of Obstetrics and Gynaecology, Amphia Hospital Breda, Langendijk 75, Breda, 4819 EV, Netherlands. hoog.pap@wxs.nl.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 13 OCT 2013

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Characteristics of included studies [ordered by study ID]
Valenzuela 2000

MethodsPlacebo-controlled, randomised trial.


Participants513 women in a multicentre trial who had preterm labour and intact membranes, with pregnancies between 20 and 33 6/7 weeks, less than or equal to 3 cm cervical dilatation, and a live fetus, who after uterine quiescence was achieved using IV atosiban (not placebo) were randomised to either placebo or atosiban maintenance therapy.

Exclusion criteria: fetal or placental abnormalities by ultrasonography, maternal indications for delivery, urinary tract infection, and overt clinical manifestations of substance abuse.


InterventionsActive drug and placebo were administered at the same volume and rate.

Atosiban group: Atosiban for maintenance was administered by a subcutaneous infusion pump to provide a continuous atosiban infusion of 6 mL/hr (30 µg/min).
Placebo group: Placebo for maintenance was administered by a subcutaneous infusion pump to provide a continuous placebo infusion of 6 mL/hr.

If subsequent IV treatment with atosiban was given for any additional episode of preterm labour, subcutaneous maintenance therapy using the assigned study treatment was recommenced if uterine quiescence was achieved. Both active drug and placebo were administered until the end of week 36 of gestation, delivery, or progression of labour requiring a tocolytic agent other than atosiban.
All women on maintenance therapy were discharged home with daily nursing contact for all. Compliance was checked by diaries kept by women and drugs used.


OutcomesThe objective of the study was to determine the safety and efficacy of maintenance therapy with the oxytocin receptor antagonist atosiban. The primary end point was the number of days from the
start of maintenance therapy until the first recurrence of labour.


NotesA sample size of 250 women in each group was estimated to be required to provide 80% power to detect an atosiban/placebo ratio of 1.3 for the mean numbers of days from the start of maintenance therapy to the first recurrence of labour.
Corticosteroids were administered for standard clinical indications. GBS protocol was unspecified
Antibiotic therapy was allowed for standard clinical conditions.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation stratified by centre, in permuted blocks of 4.

Allocation concealment (selection bias)Low riskActive drug and placebo were prepared by the R.W. Johnson Pharmaceutical Research Institute, Raritan, NJ: supplied to pharmacist in each centre in sequential pre-numbered envelopes.

Blinding (performance bias and detection bias)
All outcomes
Low riskInvestigators, study personnel and monitors were blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskPost-randomisation exclusion of one woman (placebo group) who did not receive treatment.

Selective reporting (reporting bias)Unclear riskAssessment from published reports. Further information was sought from authors but was not forthcoming.

Other biasLow riskNot apparent.

 
Comparison 1. Atosiban versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Maternal death1512Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Birth before 28 weeks174Risk Ratio (M-H, Fixed, 95% CI)0.75 [0.28, 2.01]

 3 Birth before 32 weeks1285Risk Ratio (M-H, Fixed, 95% CI)0.85 [0.47, 1.55]

 4 Birth before 37 weeks1510Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.71, 1.12]

 5 Respiratory Distress Syndrome1557Risk Ratio (M-H, Fixed, 95% CI)1.06 [0.66, 1.70]

 6 Infant death (up to 12 months)1558Risk Ratio (M-H, Fixed, 95% CI)0.74 [0.20, 2.74]

 7 Necrotising enterocolitis1557Risk Ratio (M-H, Fixed, 95% CI)2.34 [0.46, 11.93]

 8 Patent ductus arteriosius1557Risk Ratio (M-H, Fixed, 95% CI)1.17 [0.47, 2.91]

 9 Neonatal Intensive Care Unit admission1550Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.62, 1.14]

 10 Fetal death1512Risk Ratio (M-H, Fixed, 95% CI)2.89 [0.12, 70.50]

 11 Neonatal death1512Risk Ratio (M-H, Fixed, 95% CI)0.58 [0.14, 2.39]

 12 Perinatal death1512Risk Ratio (M-H, Fixed, 95% CI)0.77 [0.21, 2.83]

 13 Birth weight (grams)1558Mean Difference (IV, Fixed, 95% CI)0.10 [-131.78, 131.98]