{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T18:18:16Z","timestamp":1767896296102,"version":"3.49.0"},"reference-count":35,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"unspecified","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009128","name":"Research for Patient Benefit Programme","doi-asserted-by":"publisher","award":["NIHR206903"],"award-info":[{"award-number":["NIHR206903"]}],"id":[{"id":"10.13039\/501100009128","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,12,9]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Despite advances in maternity care, stillbirth remains a major burden. It disproportionately affects black and Asian mothers, those with obesity and women over the age of 35 years. Induction of labour may benefit these women, but there is no clear evidence to guide recommendations on optimal timing of induction because of variations in the intervention and insufficient power in primary trials for rare outcomes such as stillbirth and perinatal mortality, or to assess whether effects differ by maternal characteristics. We will conduct an individual participant data (IPD) meta-analysis of randomised trials to assess the overall and differential effect of induction of labour, according to timing of induction and maternal characteristics, on adverse perinatal and maternal outcomes. We will also rank induction of labour timing strategies by their effectiveness to inform clinical and policy decision-making.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      We will identify randomised trials on induction of labour by searching MEDLINE, CINAHL, EMBASE, BIOSIS, LILACS, Pascal, SCI, CDSR, ClinicalTrials.gov, ICTRP, ISRCTN registry, CENTRAL, DARE and Health Technology Assessment Database, without language restrictions, from inception to June 2025. Primary researchers of identified trials will be invited to join the OPTIMAL Collaboration and share the original trial data. Data integrity and trustworthiness assessment will be performed on all eligible trials. We will check each study\u2019s IPD for consistency with the original authors before standardising and harmonising the data. Study quality of included trials will be assessed by the Cochrane Risk of Bias tool. We will perform a series of one-and-two-stage random-effects meta-analyses to obtain the summary intervention effect on composite adverse perinatal outcome (stillbirth, neonatal death or severe morbidity requiring admission to neonatal unit) with 95% CIs and summary treatment\u2013covariate interactions (maternal age, ethnicity, parity, socioeconomic status, body mass index and method of conception). Heterogeneity will be summarised using tau\n                      <jats:sup>2<\/jats:sup>\n                      , I\n                      <jats:sup>2<\/jats:sup>\n                      and 95% prediction intervals for effect in a new study. Sensitivity analysis to explore robustness of statistical and clinical assumptions will be carried out. Small study effects (potential publication bias) will be investigated using funnel plots.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The study is registered on PROSPERO (CRD420251066346) and ethics approval is not required. We will disseminate findings widely to women, healthcare professionals and policymakers through academic, professional bodies and social media channels, and in peer-reviewed journals to achieve impact.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD420251066346.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-112155","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T13:40:44Z","timestamp":1767879644000},"page":"e112155","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Optimal timing of induction of labour to improve maternal and perinatal outcomes: protocol for an individual participant data and network meta-analysis"],"prefix":"10.1136","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0445-3940","authenticated-orcid":false,"given":"Hollie","family":"Meacham","sequence":"first","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Liverpool Institute of Life Course and Medical Sciences, Liverpool, England, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abraham","family":"Ona-Igbru","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Liverpool Institute of Life Course and Medical Sciences, Liverpool, England, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"McNeill","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Liverpool Institute of Life Course and Medical Sciences, Liverpool, England, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0499-9742","authenticated-orcid":false,"given":"Ruth","family":"Ajayi","sequence":"additional","affiliation":[{"name":"Patient and Public Involvement and Engagement Representative, Birmingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Pickering","sequence":"additional","affiliation":[{"name":"Patient and Public Involvement and Engagement Representative, Birmingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William A","family":"Grobman","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Brown University Warren Alpert Medical School, Providence, Rhode Island, USA"},{"name":"Care New England Health System, Providence, Rhode Island, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mairead","family":"Black","sequence":"additional","affiliation":[{"name":"Aberdeen Centre for Women\u2019s Health Research, University of Aberdeen, Aberdeen, Scotland, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asma","family":"Khalil","sequence":"additional","affiliation":[{"name":"Fetal Medicine Unit, St George\u2019s University of London, London, England, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Mccourt","sequence":"additional","affiliation":[{"name":"Centre for Maternal and Child Health Research, University of London, London, UK"},{"name":"City St George\u2019s University of London, London, England, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Miranda","sequence":"additional","affiliation":[{"name":"Clinical Biostatistics Unit, Hospital Universitario Ram\u00f3n y Cajal, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8337-550X","authenticated-orcid":false,"given":"Ben W","family":"Mol","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Monash University, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate","family":"Walker","sequence":"additional","affiliation":[{"name":"Centre for Perinatal Research, University of Nottingham School of Medicine, Nottingham, England, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amie","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of International Public Health, Liverpool School of Tropical Medicine, Liverpool, England, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Zamora","sequence":"additional","affiliation":[{"name":"Clinical Biostatistics Unit, Hospital Universitario Ram\u00f3n y Cajal, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shakila","family":"Thangaratinam","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Liverpool Institute of Life Course and Medical Sciences, Liverpool, England, UK"},{"name":"Liverpool Women\u2019s NHS Foundation Trust, Liverpool, England, UK"},{"name":"NIHR Applied Research Collaboration North West Coast, Liverpool, England, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Allotey","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Liverpool Institute of Life Course and Medical Sciences, Liverpool, England, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"2026010805402298000_16.1.e112155.1","unstructured":"Draper ES , Smith LK , Matthews RJ , et al . MBRRACE-UK perinatal mortality surveillance report: uk perinatal deaths for births from january to december 2020. 2022."},{"key":"2026010805402298000_16.1.e112155.2","unstructured":"MBRRACE-UK . Perinatal mortality surveillance: UK perinatal deaths for births from 1 january 2021 to 31 december 2021. State of the nation report. Available: https:\/\/timms.le.ac.uk\/mbrrace-uk-perinatal-mortality\/surveillance"},{"key":"2026010805402298000_16.1.e112155.3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2008.01694.x"},{"key":"2026010805402298000_16.1.e112155.4","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.070150"},{"key":"2026010805402298000_16.1.e112155.5","unstructured":"The government\u2019s 2023 mandate to NHS England. 2023. Available: https:\/\/www.gov.uk\/government\/publications\/nhs-mandate-2023\/the-governments-2023-mandate-to-nhs-england"},{"key":"2026010805402298000_16.1.e112155.6","doi-asserted-by":"publisher","DOI":"10.1089\/jwh.2015.5284"},{"key":"2026010805402298000_16.1.e112155.7","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.h3080","article-title":"Risk of recurrent stillbirth: systematic review and meta-analysis","volume":"350","author":"Lamont","year":"2015","journal-title":"BMJ"},{"key":"2026010805402298000_16.1.e112155.8","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1111\/1471-0528.16234","article-title":"Adverse pregnancy outcome and connective tissue disease: why is there a link?","volume":"127","author":"Ellwood","year":"2020","journal-title":"BJOG"},{"key":"2026010805402298000_16.1.e112155.9","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1186\/s12884-024-06986-y","article-title":"Complicated grief following the perinatal loss: a systematic review","volume":"24","author":"Zhang","year":"2024","journal-title":"BMC Pregnancy Childbirth"},{"key":"2026010805402298000_16.1.e112155.10","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1002838","article-title":"Risks of stillbirth and neonatal death with advancing gestation at term: A systematic review and meta-analysis of cohort studies of 15 million pregnancies","volume":"16","author":"Muglu","year":"2019","journal-title":"PLoS Med"},{"key":"2026010805402298000_16.1.e112155.11","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1002\/uog.17287","article-title":"Birth weight in live births and stillbirths","volume":"48","author":"Poon","year":"2016","journal-title":"Ultrasound Obstet Gynecol"},{"key":"2026010805402298000_16.1.e112155.12","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.l6131","article-title":"Induction of labour at 41 weeks versus expectant management and induction of labour at 42 weeks (SWEdish Post-term Induction Study, SWEPIS): multicentre, open label, randomised, superiority trial","volume":"367","author":"Wennerholm","year":"2019","journal-title":"BMJ"},{"key":"2026010805402298000_16.1.e112155.13","unstructured":"Inducing labour NICE guideline [NG207]. 2021. Available: https:\/\/www.nice.org.uk\/guidance\/ng207"},{"key":"2026010805402298000_16.1.e112155.14","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ejogrb.2023.07.021","article-title":"Perinatal and maternal outcomes according to timing of induction of labour: A systematic review and meta-analysis","volume":"288","author":"Jeer","year":"2023","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"2026010805402298000_16.1.e112155.15","doi-asserted-by":"publisher","DOI":"10.1186\/2046-4053-4-1"},{"key":"2026010805402298000_16.1.e112155.16","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.3656"},{"key":"2026010805402298000_16.1.e112155.17","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1111\/1471-0528.15397","article-title":"Development of a core outcome set for trials on induction of labour: an international multistakeholder Delphi study","volume":"125","author":"Dos Santos","year":"2018","journal-title":"BJOG"},{"key":"2026010805402298000_16.1.e112155.18","doi-asserted-by":"publisher","DOI":"10.3310\/hta24290"},{"key":"2026010805402298000_16.1.e112155.19","article-title":"Effect of diet and physical activity based interventions in pregnancy on gestational weight gain and pregnancy outcomes: meta-analysis of individual participant data from randomised trials","volume":"358","year":"2017","journal-title":"BMJ"},{"key":"2026010805402298000_16.1.e112155.20","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: a revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"2026010805402298000_16.1.e112155.21","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s41073-023-00130-8","article-title":"Checklist to assess Trustworthiness in RAndomised Controlled Trials (TRACT checklist): concept proposal and pilot","volume":"8","author":"Mol","year":"2023","journal-title":"Res Integr Peer Rev"},{"key":"2026010805402298000_16.1.e112155.22","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1002\/jrsm.1738","article-title":"The Individual Participant Data Integrity Tool for assessing the integrity of randomised trials","volume":"15","author":"Hunter","year":"2024","journal-title":"Res Synth Methods"},{"key":"2026010805402298000_16.1.e112155.23","article-title":"Induction of labour at or beyond 37 weeks\u2019 gestation","volume":"7","author":"Middleton","year":"2020","journal-title":"Cochrane Database Syst Rev"},{"key":"2026010805402298000_16.1.e112155.24","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.csda.2008.06.010","article-title":"Sample Sizes Required to Detect Interactions between Two Binary Fixed-Effects in a Mixed-Effects Linear Regression Model","volume":"53","author":"Leon","year":"2009","journal-title":"Comput Stat Data Anal"},{"key":"2026010805402298000_16.1.e112155.25","doi-asserted-by":"publisher","DOI":"10.7326\/M13-2886"},{"key":"2026010805402298000_16.1.e112155.26","unstructured":"Section 16.5.4: how to include multiple groups from one study. In: Cochrane handbook for systematic reviews of interventions. Available: https:\/\/training.cochrane.org\/handbook"},{"key":"2026010805402298000_16.1.e112155.27","doi-asserted-by":"publisher","DOI":"10.1177\/1536867X1501500403"},{"key":"2026010805402298000_16.1.e112155.28","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.j3932","article-title":"Multivariate and network meta-analysis of multiple outcomes and multiple treatments: rationale, concepts, and examples","volume":"358","author":"Riley","year":"2017","journal-title":"BMJ"},{"key":"2026010805402298000_16.1.e112155.29","doi-asserted-by":"publisher","DOI":"10.1177\/0962280216683570"},{"key":"2026010805402298000_16.1.e112155.30","doi-asserted-by":"publisher","DOI":"10.3310\/hta5020"},{"key":"2026010805402298000_16.1.e112155.31","unstructured":"New ambition to halve rate of stillbirths and infant deaths. 2015 Available: https:\/\/www.gov.uk\/government\/news\/new-ambition-to-halve-rate-of-stillbirths-and-infant-deaths"},{"key":"2026010805402298000_16.1.e112155.32","unstructured":"NHS England . Our business plan for 2016\/17. Available: https:\/\/www.england.nhs.uk\/wp-content\/uploads\/2016\/03\/bus-plan-16.pdf"},{"key":"2026010805402298000_16.1.e112155.33","unstructured":"NHS outcomes framework. Available: https:\/\/assets.publishing.service.gov.uk\/media\/5a749e4aed915d0e8e399a96\/nhs-out-fram-ind-may-16-comm.pdf"},{"key":"2026010805402298000_16.1.e112155.34","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/1471-0528.14972","article-title":"Healthcare and wider societal implications of stillbirth: a population-based cost-of-illness study","volume":"125","author":"Campbell","year":"2018","journal-title":"BJOG"},{"key":"2026010805402298000_16.1.e112155.35","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.c221","article-title":"Meta-analysis of individual participant data: rationale, conduct, and reporting","volume":"340","author":"Riley","year":"2010","journal-title":"BMJ"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2025-112155","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T13:40:50Z","timestamp":1767879650000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2025-112155"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,8]]},"published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1136\/bmjopen-2025-112155"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2025-112155","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]}}}