{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T03:06:15Z","timestamp":1772852775263,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pmed.1004586","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000}}],"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Stichting Stop te Vroeg Bevallen"}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"\n Background<\/jats:title>\n In absence of direct comparisons, consensus on the preferred preventive treatment for multiple pregnancies with a short cervix is lacking. Therefore, we compared the effectiveness of a cervical pessary and vaginal progesterone in the prevention of adverse perinatal outcomes and preterm birth (PTB) in women with a multiple pregnancy, no prior spontaneous PTB (sPTB) before 34 weeks\u2019 gestation, and an asymptomatic mid-trimester shortened cervix below 38\u2009mm.<\/jats:p>\n <\/jats:sec>\n \n Methods and findings<\/jats:title>\n \n This open-label, superiority, multi-centre randomised controlled trial was conducted in 20 hospitals in the Netherlands. Women with a healthy multiple pregnancy and an asymptomatic cervical length (CL) below 38\u2009mm between 16 and 22 weeks\u2019 gestation were eligible, with a target sample size of 332. Following an interim analysis, the study was halted for futility. A total of 276 multiples, including seven triplet pregnancies, were randomised 1:1 to receive either an Arabin cervical pessary (\n N<\/jats:italic>\n \u2009=\u2009138) or vaginal progesterone 200\u2009mg daily (\n N<\/jats:italic>\n \u2009=\u2009138) until 36 weeks\u2019 gestation or earlier if indicated. The primary outcome was a composite adverse perinatal outcome, with secondary outcomes including rates of (s)PTB before 24, 28, 32, 34, and 37 weeks. Predefined subgroup analyses were conducted based on CL, parity, chorionicity, and number of foetuses. Among 531 neonates (pessary\n N<\/jats:italic>\n \u2009=\u2009269, progesterone\n N<\/jats:italic>\n \u2009=\u2009262), the composite adverse perinatal outcome occurred in 19.7% of neonates in the pessary group versus 13.7% in the progesterone group (crude RR 1.43; 95% CI [0.85,2.4],\n p<\/jats:italic>\n \u2009=\u20090.18). The rates of (s)PTB were not significantly different between groups. In the subgroup with a CL of \u226425\u2009mm, no significant difference in the composite perinatal outcome was found (41.1% versus 34.7%, RR 1.18; 95% CI [0.60,2.33], interaction\n p<\/jats:italic>\n \u2009=\u20090.63). However, among nulliparous women, the composite outcome was more frequent in the pessary group compared to progesterone (30.0% versus 15.9%, RR 1.88; 95% CI [1.03,3.43], interaction\n p<\/jats:italic>\n \u2009=\u20090.93). The study\u2019s main limitations include the inability to blind interventions, potentially introducing bias, and low self-reported medication compliance in the progesterone group, which may have led to overestimated adherence and underestimated progesterone\u2019s preventive potential in the per-protocol analysis.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n In women with multiple pregnancies and a midtrimester short cervix below 38\u2009mm, we found no superiority of a cervical pessary compared to vaginal progesterone the prevention of perinatal complications. While progesterone may have a modest effect, future studies should focus on other interventions in multiple pregnancies such as a cerclage, both ultrasound- and physical examination-indicated.<\/jats:p>\n <\/jats:sec>\n \n Trial registration<\/jats:title>\n \n This trial was registered at the International Clinical Trial Registry Platform (ICTRP, EUCTR2013-002884-24-NL,\n https:\/\/trialsearch.who.int\/Trial2.aspx?TrialID=EUCTR2013-002884-24-NL<\/jats:ext-link>\n ).\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pmed.1004586","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T18:31:26Z","timestamp":1762194686000},"page":"e1004586","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cervical pessary versus vaginal progesterone in women with a multiple pregnancy and a short cervix: A randomised controlled trial"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9417-4180","authenticated-orcid":true,"given":"Charlotte E.","family":"van Dijk","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2083-0285","authenticated-orcid":true,"given":"Annabelle L.","family":"van Gils","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maud D.","family":"van Zijl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bouchra","family":"Koullali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6979-1347","authenticated-orcid":true,"given":"Marijke C.","family":"van der Weide","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eline S.","family":"van den Akker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenda J.","family":"Hermsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joris","family":"van Drongelen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjon A.","family":"de Boer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilhelmina M.","family":"van Baal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7968-8263","authenticated-orcid":true,"given":"Karlijn C.","family":"Vollebregt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flip W.","family":"van der Made","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3915-8609","authenticated-orcid":true,"given":"Sanne J.","family":"Gordijn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marieke","family":"Sueters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lia D. 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