{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T07:03:36Z","timestamp":1790406216309,"version":"4.1.0"},"reference-count":24,"publisher":"National Institute for Health and Care Research","issue":"35","license":[{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100001922","name":"Efficacy and Mechanism Evaluation programme","doi-asserted-by":"publisher","award":["09\/800\/27"],"award-info":[{"award-number":["09\/800\/27"]}],"id":[{"id":"10.13039\/501100001922","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\">\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Progesterone prophylaxis is widely used to prevent preterm birth but is not licensed and there is little information on long-term outcome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-2\">\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To determine the effect of progesterone prophylaxis in women at high risk of preterm birth on obstetric, neonatal and childhood outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-3\">\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Double-blind, randomised placebo-controlled trial.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-4\">\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Obstetric units in the UK and Europe between February 2009 and April 2013.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-5\">\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>Women with a singleton pregnancy who are at high risk of preterm birth because of either a positive fibronectin test or a negative fibronectin test, and either previous spontaneous birth at \u2264\u200934 weeks<jats:sup>+0<\/jats:sup> of gestation or a cervical length of \u2264\u200925 mm.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-6\">\n                  <jats:title>Interventions<\/jats:title>\n                  <jats:p>Fibronectin test at 18<jats:sup>+0<\/jats:sup> to 23<jats:sup>+0<\/jats:sup> weeks of pregnancy to determine risk of preterm birth. Eligible women were allocated (using a web-based randomisation portal) to 200\u2009mg of progesterone or placebo, taken vaginally daily from 22<jats:sup>+0<\/jats:sup> to 24<jats:sup>+0<\/jats:sup> until 34<jats:sup>+0<\/jats:sup> weeks\u2019 gestation. Participants, caregivers and those assessing the outcomes were blinded to group assignment until data collection was complete.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-7\">\n                  <jats:title>Main outcome measures<\/jats:title>\n                  <jats:p>There were three primary outcomes, as follows: (1) obstetric \u2013 fetal death or delivery before 34<jats:sup>+0<\/jats:sup> weeks\u2019 gestation; (2) neonatal \u2013 a composite of death, brain injury on ultrasound scan (according to specific criteria in the protocol) and bronchopulmonary dysplasia; and (3) childhood \u2013 the Bayley-III cognitive composite score at 22\u201326 months of age.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-8\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In total, 96 out of 600 (16%) women in the progesterone group and 108 out of 597 (18%) women in the placebo group had the primary obstetric outcome [odds ratio (OR) 0.86, 95% confidence interval (CI) 0.61 to 1.22]. Forty-six out of 589 (8%) babies of women in the progesterone group and 62 out of 587 (11%) babies of women in the placebo group experienced the primary neonatal outcome [OR 0.72, 95% CI 0.44 to 1.17]. The mean Bayley-III cognitive composite score of the children at 2 years of age was 97.3 points [standard deviation (SD) 17.9 points; <jats:italic>n<\/jats:italic>\u2009=\u2009430] in the progesterone group and 97.7 points (SD 17.5 points; <jats:italic>n<\/jats:italic>\u2009=\u2009439) in the placebo group (difference in means \u20130.48, 95% CI \u20132.77 to 1.81).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-9\">\n                  <jats:title>Limitations<\/jats:title>\n                  <jats:p>Overall compliance with the intervention was 69%.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-10\">\n                  <jats:title>Harms<\/jats:title>\n                  <jats:p>There were no major harms, although there was a trend of more deaths from trial entry to 2 years in the progesterone group (20\/600) than in the placebo group (16\/598) (OR 1.26, 95% CI 0.65 to 2.42).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-11\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In this study, progesterone had no significant beneficial or harmful effects on the primary obstetric, neonatal or childhood outcomes.The OPPTIMUM trial is now complete. We intend to participate in a comprehensive individual patient-level data meta-analysis examining women with a singleton pregnancy with a variety of risk factors for preterm birth.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-12\">\n                  <jats:title>Trial registration<\/jats:title>\n                  <jats:p>Current Controlled Trials ISRCTN14568373.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-13\">\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>This trial was funded by the Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC\u2013NIHR partnership.<\/jats:p>\n               <\/jats:sec>","DOI":"10.3310\/hta22350","type":"journal-article","created":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T11:40:21Z","timestamp":1530013221000},"page":"1-304","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["Does progesterone prophylaxis to prevent preterm labour improve outcome? 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Health and Wellbeing, University of Glasgow, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5273-3132","authenticated-orcid":true,"given":"Andrew","family":"Shennan","sequence":"additional","affiliation":[{"name":"Women\u2019s Health Academic Centre, King\u2019s College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6253-4919","authenticated-orcid":true,"given":"Philip R","family":"Bennett","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynaecology, Department of Surgery and Cancer, Imperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7613-0408","authenticated-orcid":true,"given":"Steven","family":"Thornton","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynaecology (Barts), Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7897-7987","authenticated-orcid":true,"given":"Stephen C","family":"Robson","sequence":"additional","affiliation":[{"name":"The Medical School, University of Newcastle, Newcastle, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7262-7000","authenticated-orcid":true,"given":"Alex","family":"McConnachie","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3121-6050","authenticated-orcid":true,"given":"Stavros","family":"Petrou","sequence":"additional","affiliation":[{"name":"Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, 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