Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis

Jane E Norman, Fiona Mackenzie, Philip Owen, Helen Mactier, Kevin Hanretty, Sarah Cooper, Andrew Calder, Gary Mires, Peter Danielian, Stephen Sturgiss, Graeme MacLennan, Graham Tydeman, Steven Thornton, Bill Martin, James G Thornton, James P Neilson, John Norrie

Research output: Contribution to journalArticle

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Abstract

Background
Women with twin pregnancy are at high risk for spontaneous preterm delivery. Progesterone seems to be effective in reducing preterm birth in selected high-risk singleton pregnancies, albeit with no significant reduction in perinatal mortality and little evidence of neonatal benefit. We investigated the use of progesterone for prevention of preterm birth in twin pregnancy.

Methods
In this double-blind, placebo-controlled trial, 500 women with twin pregnancy were recruited from nine UK National Health Service clinics specialising in the management of twin pregnancy. Women were randomised, by permuted blocks of randomly mixed sizes, either to daily vaginal progesterone gel 90 mg (n=250) or to placebo gel (n=250) for 10 weeks from 24 weeks' gestation. All study personnel and participants were masked to treatment assignment for the duration of the study. The primary outcome was delivery or intrauterine death before 34 weeks' gestation. Analysis was by intention to treat. Additionally we undertook a meta-analysis of published and unpublished data to establish the efficacy of progesterone in prevention of early (<34 weeks' gestation) preterm birth or intrauterine death in women with twin pregnancy. This study is registered, number ISRCTN35782581.

Findings
Three participants in each group were lost to follow-up, leaving 247 analysed per group. The combined proportion of intrauterine death or delivery before 34 weeks of pregnancy was 24·7% (61/247) in the progesterone group and 19·4% (48/247) in the placebo group (odds ratio [OR] 1·36, 95% CI 0·89–2·09; p=0·16). The rate of adverse events did not differ between the two groups. The meta-analysis confirmed that progesterone does not prevent early preterm birth in women with twin pregnancy (pooled OR 1·16, 95% CI 0·89–1·51).

Interpretation
Progesterone, administered vaginally, does not prevent preterm birth in women with twin pregnancy.
Original languageEnglish
Pages (from-to)2034-2040
Number of pages7
JournalThe Lancet
Volume373
Issue number9680
Early online date11 Jun 2009
DOIs
Publication statusPublished - 13 Jun 2009

Fingerprint

Twin Pregnancy
Premature Birth
Progesterone
Meta-Analysis
Placebos
Pregnancy
Odds Ratio
Foams and Jellies Vaginal Creams
High-Risk Pregnancy
Intention to Treat Analysis
Perinatal Mortality
Lost to Follow-Up
National Health Programs
Gels

Keywords

  • administration, intravaginal
  • adolescent
  • adult
  • delivery, obstetric
  • double-blind method
  • female
  • fetal death
  • follow-up studies
  • gels
  • Great Britain
  • humans
  • likelihood functions
  • linear models
  • logistic models
  • middle aged
  • patient selection
  • pregnancy
  • pregnancy outcome
  • pregnancy, high-risk
  • pregnancy, multiple
  • premature birth
  • progesterone
  • progestins
  • treatment failure
  • twins
  • young adult

Cite this

Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT) : a randomised, double-blind, placebo-controlled study and meta-analysis. / Norman, Jane E; Mackenzie, Fiona; Owen, Philip; Mactier, Helen; Hanretty, Kevin; Cooper, Sarah; Calder, Andrew; Mires, Gary; Danielian, Peter; Sturgiss, Stephen; MacLennan, Graeme; Tydeman, Graham; Thornton, Steven; Martin, Bill; Thornton, James G; Neilson, James P; Norrie, John.

In: The Lancet, Vol. 373, No. 9680, 13.06.2009, p. 2034-2040.

Research output: Contribution to journalArticle

Norman, JE, Mackenzie, F, Owen, P, Mactier, H, Hanretty, K, Cooper, S, Calder, A, Mires, G, Danielian, P, Sturgiss, S, MacLennan, G, Tydeman, G, Thornton, S, Martin, B, Thornton, JG, Neilson, JP & Norrie, J 2009, 'Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis', The Lancet, vol. 373, no. 9680, pp. 2034-2040. https://doi.org/10.1016/S0140-6736(09)60947-8
Norman, Jane E ; Mackenzie, Fiona ; Owen, Philip ; Mactier, Helen ; Hanretty, Kevin ; Cooper, Sarah ; Calder, Andrew ; Mires, Gary ; Danielian, Peter ; Sturgiss, Stephen ; MacLennan, Graeme ; Tydeman, Graham ; Thornton, Steven ; Martin, Bill ; Thornton, James G ; Neilson, James P ; Norrie, John. / Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT) : a randomised, double-blind, placebo-controlled study and meta-analysis. In: The Lancet. 2009 ; Vol. 373, No. 9680. pp. 2034-2040.
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T2 - a randomised, double-blind, placebo-controlled study and meta-analysis

AU - Norman, Jane E

AU - Mackenzie, Fiona

AU - Owen, Philip

AU - Mactier, Helen

AU - Hanretty, Kevin

AU - Cooper, Sarah

AU - Calder, Andrew

AU - Mires, Gary

AU - Danielian, Peter

AU - Sturgiss, Stephen

AU - MacLennan, Graeme

AU - Tydeman, Graham

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N2 - BackgroundWomen with twin pregnancy are at high risk for spontaneous preterm delivery. Progesterone seems to be effective in reducing preterm birth in selected high-risk singleton pregnancies, albeit with no significant reduction in perinatal mortality and little evidence of neonatal benefit. We investigated the use of progesterone for prevention of preterm birth in twin pregnancy.MethodsIn this double-blind, placebo-controlled trial, 500 women with twin pregnancy were recruited from nine UK National Health Service clinics specialising in the management of twin pregnancy. Women were randomised, by permuted blocks of randomly mixed sizes, either to daily vaginal progesterone gel 90 mg (n=250) or to placebo gel (n=250) for 10 weeks from 24 weeks' gestation. All study personnel and participants were masked to treatment assignment for the duration of the study. The primary outcome was delivery or intrauterine death before 34 weeks' gestation. Analysis was by intention to treat. Additionally we undertook a meta-analysis of published and unpublished data to establish the efficacy of progesterone in prevention of early (<34 weeks' gestation) preterm birth or intrauterine death in women with twin pregnancy. This study is registered, number ISRCTN35782581.FindingsThree participants in each group were lost to follow-up, leaving 247 analysed per group. The combined proportion of intrauterine death or delivery before 34 weeks of pregnancy was 24·7% (61/247) in the progesterone group and 19·4% (48/247) in the placebo group (odds ratio [OR] 1·36, 95% CI 0·89–2·09; p=0·16). The rate of adverse events did not differ between the two groups. The meta-analysis confirmed that progesterone does not prevent early preterm birth in women with twin pregnancy (pooled OR 1·16, 95% CI 0·89–1·51).InterpretationProgesterone, administered vaginally, does not prevent preterm birth in women with twin pregnancy.

AB - BackgroundWomen with twin pregnancy are at high risk for spontaneous preterm delivery. Progesterone seems to be effective in reducing preterm birth in selected high-risk singleton pregnancies, albeit with no significant reduction in perinatal mortality and little evidence of neonatal benefit. We investigated the use of progesterone for prevention of preterm birth in twin pregnancy.MethodsIn this double-blind, placebo-controlled trial, 500 women with twin pregnancy were recruited from nine UK National Health Service clinics specialising in the management of twin pregnancy. Women were randomised, by permuted blocks of randomly mixed sizes, either to daily vaginal progesterone gel 90 mg (n=250) or to placebo gel (n=250) for 10 weeks from 24 weeks' gestation. All study personnel and participants were masked to treatment assignment for the duration of the study. The primary outcome was delivery or intrauterine death before 34 weeks' gestation. Analysis was by intention to treat. Additionally we undertook a meta-analysis of published and unpublished data to establish the efficacy of progesterone in prevention of early (<34 weeks' gestation) preterm birth or intrauterine death in women with twin pregnancy. This study is registered, number ISRCTN35782581.FindingsThree participants in each group were lost to follow-up, leaving 247 analysed per group. The combined proportion of intrauterine death or delivery before 34 weeks of pregnancy was 24·7% (61/247) in the progesterone group and 19·4% (48/247) in the placebo group (odds ratio [OR] 1·36, 95% CI 0·89–2·09; p=0·16). The rate of adverse events did not differ between the two groups. The meta-analysis confirmed that progesterone does not prevent early preterm birth in women with twin pregnancy (pooled OR 1·16, 95% CI 0·89–1·51).InterpretationProgesterone, administered vaginally, does not prevent preterm birth in women with twin pregnancy.

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KW - adult

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KW - Great Britain

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KW - logistic models

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KW - pregnancy outcome

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