title: Cervical pessaries to prevent preterm birth in women with a multiple pregnancy: a per-protocol analysis of a randomized clinical trial.
abstract: BACKGROUND
  We recently showed that a cervical pessary prevents preterm birth and reduces poor neonatal outcomes in women with a twin pregnancy and a short cervix (<38 mm). The objective of this study was to evaluate the full potential treatment effect of the pessary in the whole group and in women with a short cervix.
  
  
  METHODS
  We performed a per-protocol analysis of a multicenter randomized controlled trial (ProTWIN trial, NTR1858) where we excluded women who were allocated to the pessary but never had it placed. Women who had the pessary removed before 36 gestational weeks and did not deliver within 7 days after removal, were excluded. Analyses were performed on all women and in those with a cervical length <38 mm.
  
  
  RESULTS
  In 23 (6%) women the pessary was not placed. In women with a cervical length <38 mm (25th percentile) the pessary reduced poor perinatal outcome (relative risk 0.32, 95% confidence interval 0.13-0.78) and birth at <32 weeks (relative risk 0.41, 95% confidence interval 0.20-0.87). After excluding 47 (12%) women, the time to delivery was longer in the pessary group than in the control group (whole group: hazard ratio 0.68, 95% confidence interval 0.55-0.82, cervical length <38 mm: hazard ratio 0.35, 95% confidence interval 0.22-0.57).
  
  
  CONCLUSIONS
  The analysis confirms the principal findings of the intention-to-treat analysis. Time to delivery was longer in the pessary group than in the control group when censored data were used. This implies the pessary should not be removed until labor is evident.
authors.affiliation: Obstetrics and Gynecology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Sophie M S
authors.identifier: http://orcid.org/0000-0002-3214-2076
authors.initials: SM
authors.lastname: Liem
authors.affiliation: Obstetrics and Gynecology, Academic Medical Center, Amsterdam, the Netherlands.|Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.|Stanford Prevention Research Center, Stanford University, Stanford, CA, USA.
authors.forename: Ewoud
authors.identifier: http://orcid.org/0000-0002-9548-3214
authors.initials: E
authors.lastname: Schuit
authors.affiliation: Obstetrics and Gynecology, Onze Lieve Vrouwe Gasthuis Hospital, Amsterdam, the Netherlands.
authors.forename: Mariëlle G
authors.identifier: http://orcid.org/0000-0002-3020-8908
authors.initials: MG
authors.lastname: van Pampus
authors.affiliation: Department of Obstetrics and Gynecology, Academic Hospital Maastricht, Maastricht, the Netherlands.
authors.forename: Marjo
authors.identifier: http://orcid.org/0000-0003-4866-559X
authors.initials: M
authors.lastname: van Melick
authors.affiliation: Obstetrics and Gynecology, Atrium Hospital, Heerlen, the Netherlands.
authors.forename: Maurice
authors.identifier: http://orcid.org/0000-0001-7353-7894
authors.initials: M
authors.lastname: Monfrance
authors.affiliation: Obstetrics and Gynecology, Atrium Hospital, Heerlen, the Netherlands.
authors.forename: Josje
authors.identifier: http://orcid.org/0000-0003-0107-2332
authors.initials: J
authors.lastname: Langenveld
authors.affiliation: Robinson Research Institute, School for Pediatrics and Reproductive Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Ben W J
authors.identifier: http://orcid.org/0000-0001-8337-550X
authors.initials: BW
authors.lastname: Mol
authors.affiliation: Obstetrics and Gynecology, Onze Lieve Vrouwe Gasthuis Hospital, Amsterdam, the Netherlands.
authors.forename: Dick
authors.identifier: http://orcid.org/0000-0003-3470-9344
authors.initials: D
authors.lastname: Bekedam
mesh_terms: D000328:Adult; D054791:Cervical Length Measurement; D002584:Cervix Uteri; D020878:Device Removal; D005260:Female; D006801:Humans; D009426:Netherlands; D010570:Pessaries; D011247:Pregnancy; D011256:Pregnancy Outcome; D011272:Pregnancy, Multiple; D047928:Premature Birth / Q000517:prevention & control*
keywords: Preterm birth; cervical pessaries; delivery; multiple pregnancies; pregnancy