Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2): an open-label randomised trial and updated meta-analysis.

Research output: Contribution to journalArticlepeer-review

Standard

Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2) : an open-label randomised trial and updated meta-analysis. / Norman, Jane E; Norrie, John; MacLennan, Graeme; Cooper, David; Whyte, Sonia; Chowdhry, Sue; Cunningham Burley, Sarah; Mei, Xue; Smith, Joel B E ; Shennan, Andrew ; Robson, Stephen C; Thornton, Steven; Kilby, Mark; Marlow, Neil; Stock, Sarah J; Bennett, Phillip; Denton, Jane.

In: PLoS Medicine, Vol. 18, No. 3, e1003506, 29.03.2021.

Research output: Contribution to journalArticlepeer-review

Harvard

Norman, JE, Norrie, J, MacLennan, G, Cooper, D, Whyte, S, Chowdhry, S, Cunningham Burley, S, Mei, X, Smith, JBE, Shennan, A, Robson, SC, Thornton, S, Kilby, M, Marlow, N, Stock, SJ, Bennett, P & Denton, J 2021, 'Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2): an open-label randomised trial and updated meta-analysis.', PLoS Medicine, vol. 18, no. 3, e1003506. https://doi.org/10.1371/journal.pmed.1003506

APA

Norman, J. E., Norrie, J., MacLennan, G., Cooper, D., Whyte, S., Chowdhry, S., Cunningham Burley, S., Mei, X., Smith, J. B. E., Shennan, A., Robson, S. C., Thornton, S., Kilby, M., Marlow, N., Stock, S. J., Bennett, P., & Denton, J. (2021). Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2): an open-label randomised trial and updated meta-analysis. PLoS Medicine, 18(3), [e1003506]. https://doi.org/10.1371/journal.pmed.1003506

Vancouver

Author

Norman, Jane E ; Norrie, John ; MacLennan, Graeme ; Cooper, David ; Whyte, Sonia ; Chowdhry, Sue ; Cunningham Burley, Sarah ; Mei, Xue ; Smith, Joel B E ; Shennan, Andrew ; Robson, Stephen C ; Thornton, Steven ; Kilby, Mark ; Marlow, Neil ; Stock, Sarah J ; Bennett, Phillip ; Denton, Jane. / Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2) : an open-label randomised trial and updated meta-analysis. In: PLoS Medicine. 2021 ; Vol. 18, No. 3.

Bibtex

@article{7ec610f9350f4e2bb3487fa1c4a73f8a,
title = "Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2): an open-label randomised trial and updated meta-analysis.",
abstract = "Background: Preterm-labour-associated preterm birth is a common cause of perinatal mortality and morbidity in twin pregnancy. We aimed to test the hypothesis that the Arabin pessary would reduce preterm-labour-associated preterm birth by 40% or greater in women with a twin pregnancy and a short cervix.Methods and findings: We conducted an open-label randomised controlled trial in 57 hospital antenatal clinics in the UK and Europe. From 1 April 2015 to 14 February 2019, 2,228 women with a twin pregnancy underwent cervical length screening between 18 weeks 0 days and 20 weeks 6 days of gestation. In total, 503 women with cervical length ≤ 35 mm were randomly assigned to pessary in addition to standard care (n = 250, mean age 32.4 years, mean cervical length 29 mm, with pessary inserted in 230 women [92.0%]) or standard care alone (n = 253, mean age 32.7 years, mean cervical length 30 mm). The pessary was inserted before 21 completed weeks of gestation and removed at between 35 and 36 weeks or before birth if earlier. The primary obstetric outcome, spontaneous onset of labour and birth before 34 weeks 0 days of gestation, was present in 46/250 (18.4%) in the pessary group compared to 52/253 (20.6%) following standard care alone (adjusted odds ratio [aOR] 0.87 [95% CI 0.55–1.38], p = 0.54). The primary neonatal outcome—a composite of any of stillbirth, neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis, or proven sepsis, from birth to 28 days after the expected date of delivery—was present in 67/500 infants (13.4%) in the pessary group compared to 76/506 (15.0%) following standard care alone (aOR 0.86 [95% CI 0.54–1.36], p = 0.50). The positive and negative likelihood ratios of a short cervix (≤35 mm) to predict preterm birth before 34 weeks were 2.14 and 0.83, respectively. A meta-analysis of data from existing publications (4 studies, 313 women) and from STOPPIT-2 indicated that a cervical pessary does not reduce preterm birth before 34 weeks in women with a short cervix (risk ratio 0.74 [95% CI 0.50–1.11], p = 0.15). No women died in either arm of the study; 4.4% of babies in the Arabin pessary group and 5.5% of babies in the standard treatment group died in utero or in the neonatal period (p = 0.53). Study limitations include lack of power to exclude a smaller than 40% reduction in preterm labour associated preterm birth, and to be conclusive about subgroup analyses.Conclusions: These results led us to reject our hypothesis that the Arabin pessary would reduce the risk of the primary outcome by 40%. Smaller treatment effects cannot be ruled out.Trial registration: ClinicalTrials.gov ISRCTN 02235181.ClinicalTrials.gov NCT02235181.",
author = "Norman, {Jane E} and John Norrie and Graeme MacLennan and David Cooper and Sonia Whyte and Sue Chowdhry and {Cunningham Burley}, Sarah and Xue Mei and Smith, {Joel B E} and Andrew Shennan and Robson, {Stephen C} and Steven Thornton and Mark Kilby and Neil Marlow and Stock, {Sarah J} and Phillip Bennett and Jane Denton",
note = "Funding: This study was funded by the National Institute for Health Research (NIHR nihr.ac.uk) Health Technology Assessment Programme (project reference HTA 13/04/22). The funder had no role in study design, data collection, data analysis, data interpretation or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. JEN, JN, SCB, JBES, AS, SCR, ST, MDK, NM, SJS, PRB and JD were grant holders on HTA 13/04/22. A portion of the salaries of all authors were claimed as direct or indirect costs from HTA 13/04/22 by the authors{\textquoteright} employing institution. During this research MDK received and was part funded by a grant from The Richard And Jack Wiseman Trust https://www.wisemantrust.co.uk. JBES, AS and PRB are funded by the National Institute for Health Research Biomedical Research Centres at the Universities of Oxford (grant number NIHR-BRC-1215-20008 nihr.ac.uk nihr.ac.uk), Kings College London and Imperial College London respectively. The funder had no role in this study design, data collection, data analysis, data interpretation, writing or decision to submit this report.",
year = "2021",
month = mar,
day = "29",
doi = "10.1371/journal.pmed.1003506",
language = "English",
volume = "18",
journal = "PLoS Medicine",
issn = "1549-1277",
publisher = "Public Library of Science (PLOS)",
number = "3",

}

RIS

TY - JOUR

T1 - Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2)

T2 - an open-label randomised trial and updated meta-analysis.

AU - Norman, Jane E

AU - Norrie, John

AU - MacLennan, Graeme

AU - Cooper, David

AU - Whyte, Sonia

AU - Chowdhry, Sue

AU - Cunningham Burley, Sarah

AU - Mei, Xue

AU - Smith, Joel B E

AU - Shennan, Andrew

AU - Robson, Stephen C

AU - Thornton, Steven

AU - Kilby, Mark

AU - Marlow, Neil

AU - Stock, Sarah J

AU - Bennett, Phillip

AU - Denton, Jane

N1 - Funding: This study was funded by the National Institute for Health Research (NIHR nihr.ac.uk) Health Technology Assessment Programme (project reference HTA 13/04/22). The funder had no role in study design, data collection, data analysis, data interpretation or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. JEN, JN, SCB, JBES, AS, SCR, ST, MDK, NM, SJS, PRB and JD were grant holders on HTA 13/04/22. A portion of the salaries of all authors were claimed as direct or indirect costs from HTA 13/04/22 by the authors’ employing institution. During this research MDK received and was part funded by a grant from The Richard And Jack Wiseman Trust https://www.wisemantrust.co.uk. JBES, AS and PRB are funded by the National Institute for Health Research Biomedical Research Centres at the Universities of Oxford (grant number NIHR-BRC-1215-20008 nihr.ac.uk nihr.ac.uk), Kings College London and Imperial College London respectively. The funder had no role in this study design, data collection, data analysis, data interpretation, writing or decision to submit this report.

PY - 2021/3/29

Y1 - 2021/3/29

N2 - Background: Preterm-labour-associated preterm birth is a common cause of perinatal mortality and morbidity in twin pregnancy. We aimed to test the hypothesis that the Arabin pessary would reduce preterm-labour-associated preterm birth by 40% or greater in women with a twin pregnancy and a short cervix.Methods and findings: We conducted an open-label randomised controlled trial in 57 hospital antenatal clinics in the UK and Europe. From 1 April 2015 to 14 February 2019, 2,228 women with a twin pregnancy underwent cervical length screening between 18 weeks 0 days and 20 weeks 6 days of gestation. In total, 503 women with cervical length ≤ 35 mm were randomly assigned to pessary in addition to standard care (n = 250, mean age 32.4 years, mean cervical length 29 mm, with pessary inserted in 230 women [92.0%]) or standard care alone (n = 253, mean age 32.7 years, mean cervical length 30 mm). The pessary was inserted before 21 completed weeks of gestation and removed at between 35 and 36 weeks or before birth if earlier. The primary obstetric outcome, spontaneous onset of labour and birth before 34 weeks 0 days of gestation, was present in 46/250 (18.4%) in the pessary group compared to 52/253 (20.6%) following standard care alone (adjusted odds ratio [aOR] 0.87 [95% CI 0.55–1.38], p = 0.54). The primary neonatal outcome—a composite of any of stillbirth, neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis, or proven sepsis, from birth to 28 days after the expected date of delivery—was present in 67/500 infants (13.4%) in the pessary group compared to 76/506 (15.0%) following standard care alone (aOR 0.86 [95% CI 0.54–1.36], p = 0.50). The positive and negative likelihood ratios of a short cervix (≤35 mm) to predict preterm birth before 34 weeks were 2.14 and 0.83, respectively. A meta-analysis of data from existing publications (4 studies, 313 women) and from STOPPIT-2 indicated that a cervical pessary does not reduce preterm birth before 34 weeks in women with a short cervix (risk ratio 0.74 [95% CI 0.50–1.11], p = 0.15). No women died in either arm of the study; 4.4% of babies in the Arabin pessary group and 5.5% of babies in the standard treatment group died in utero or in the neonatal period (p = 0.53). Study limitations include lack of power to exclude a smaller than 40% reduction in preterm labour associated preterm birth, and to be conclusive about subgroup analyses.Conclusions: These results led us to reject our hypothesis that the Arabin pessary would reduce the risk of the primary outcome by 40%. Smaller treatment effects cannot be ruled out.Trial registration: ClinicalTrials.gov ISRCTN 02235181.ClinicalTrials.gov NCT02235181.

AB - Background: Preterm-labour-associated preterm birth is a common cause of perinatal mortality and morbidity in twin pregnancy. We aimed to test the hypothesis that the Arabin pessary would reduce preterm-labour-associated preterm birth by 40% or greater in women with a twin pregnancy and a short cervix.Methods and findings: We conducted an open-label randomised controlled trial in 57 hospital antenatal clinics in the UK and Europe. From 1 April 2015 to 14 February 2019, 2,228 women with a twin pregnancy underwent cervical length screening between 18 weeks 0 days and 20 weeks 6 days of gestation. In total, 503 women with cervical length ≤ 35 mm were randomly assigned to pessary in addition to standard care (n = 250, mean age 32.4 years, mean cervical length 29 mm, with pessary inserted in 230 women [92.0%]) or standard care alone (n = 253, mean age 32.7 years, mean cervical length 30 mm). The pessary was inserted before 21 completed weeks of gestation and removed at between 35 and 36 weeks or before birth if earlier. The primary obstetric outcome, spontaneous onset of labour and birth before 34 weeks 0 days of gestation, was present in 46/250 (18.4%) in the pessary group compared to 52/253 (20.6%) following standard care alone (adjusted odds ratio [aOR] 0.87 [95% CI 0.55–1.38], p = 0.54). The primary neonatal outcome—a composite of any of stillbirth, neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis, or proven sepsis, from birth to 28 days after the expected date of delivery—was present in 67/500 infants (13.4%) in the pessary group compared to 76/506 (15.0%) following standard care alone (aOR 0.86 [95% CI 0.54–1.36], p = 0.50). The positive and negative likelihood ratios of a short cervix (≤35 mm) to predict preterm birth before 34 weeks were 2.14 and 0.83, respectively. A meta-analysis of data from existing publications (4 studies, 313 women) and from STOPPIT-2 indicated that a cervical pessary does not reduce preterm birth before 34 weeks in women with a short cervix (risk ratio 0.74 [95% CI 0.50–1.11], p = 0.15). No women died in either arm of the study; 4.4% of babies in the Arabin pessary group and 5.5% of babies in the standard treatment group died in utero or in the neonatal period (p = 0.53). Study limitations include lack of power to exclude a smaller than 40% reduction in preterm labour associated preterm birth, and to be conclusive about subgroup analyses.Conclusions: These results led us to reject our hypothesis that the Arabin pessary would reduce the risk of the primary outcome by 40%. Smaller treatment effects cannot be ruled out.Trial registration: ClinicalTrials.gov ISRCTN 02235181.ClinicalTrials.gov NCT02235181.

U2 - 10.1371/journal.pmed.1003506

DO - 10.1371/journal.pmed.1003506

M3 - Article

VL - 18

JO - PLoS Medicine

JF - PLoS Medicine

SN - 1549-1277

IS - 3

M1 - e1003506

ER -