{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T17:49:35Z","timestamp":1782150575843,"version":"3.54.5"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sasakawa Health Foundation","award":["2025-07"],"award-info":[{"award-number":["2025-07"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>International guidelines, such as those from the WHO, recommend limiting the duration of tocolysis to up to 48 hours in order to provide a window for antenatal corticosteroid administration and maternal transfer. However, reports from multiple countries indicate that tocolysis is being performed for 48 hours or longer in actual clinical settings. This study used nationwide data in Japan over an 11-year period to investigate changes in tocolytic protocol and identify factors associated with tocolysis within 48 hours.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using the Diagnosis Procedure Combination database, we analyzed data from 156,356 pregnant women who received ritodrine infusion for preterm labor between April 2012 and March 2023. To accommodate day-based administrative data, we defined acute tocolysis (AT) as \u22642 and maintenance tocolysis (MT) as \u22654 days of treatment. Annual trends in AT utilization rates were examined, and logistic regression analysis was performed to identify factors associated with AT, including institutional characteristics, regional differences, and obstetric complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The rate of AT utilization increased from 15.73% to 23.74% over the study period, as did variation among hospitals. University hospitals (adjusted odds ratio [aOR] = 1.16), perinatal centers (aOR = 1.12), preterm premature rupture of membranes (aOR = 3.18), and pregnancy-induced hypertension (aOR = 1.52) were associated with AT, while concomitant use of magnesium sulfate hydrate (aOR = 0.91), multiple fetuses (aOR = 0.64), and placenta previa (aOR = 0.67) were negatively associated with AT utilization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>While AT utilization has increased over time, significant disparities between facilities remain. These findings suggest that the choice of tocolytic protocol is not determined by evidence alone, but is complexly influenced by institutional roles, regional healthcare systems, and specific maternal complications. This study highlights the importance of understanding these multifaceted factors to optimize treatment strategies that balance international standards with the practicalities of individualized patient care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0351293","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T17:22:06Z","timestamp":1782148926000},"page":"e0351293","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Trends and determinants of acute tocolysis implementation in Japan, 2012\u20132023: An 11-year nationwide retrospective cohort study"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7765-3988","authenticated-orcid":true,"given":"Mikayo","family":"Toba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1855-4584","authenticated-orcid":true,"given":"Rie","family":"Oi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutsuko","family":"Moriwaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Kakehashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Fudono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1894-0290","authenticated-orcid":true,"given":"Kiyohide","family":"Fushimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyuki","family":"Miyasaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"pone.0351293.ref001","author":"WHO"},{"key":"pone.0351293.ref002","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/1742-4755-11-82","article-title":"UNICEF Report: Enormous progress in child survival but greater focus on newborns urgently needed","volume":"11","author":"T Wardlaw","year":"2014","journal-title":"Reprod Health"},{"key":"pone.0351293.ref003","volume-title":"Neonatal respiratory distress syndrome","author":"S Yadav","year":"2021"},{"issue":"3","key":"pone.0351293.ref004","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1055\/s-0035-1571202","article-title":"Short- and long-term outcomes for extremely preterm infants","volume":"33","author":"RM Patel","year":"2016","journal-title":"Am J Perinatol"},{"issue":"4","key":"pone.0351293.ref005","article-title":"Hearing loss by week of gestation and birth weight in very preterm neonates","volume":"166","author":"Dutch Neonatal Intensive Care Unit Neonatal Hearing Screening Working Group","year":"2015","journal-title":"J Pediatr"},{"issue":"10409","key":"pone.0351293.ref006","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/S0140-6736(23)00878-4","article-title":"National, regional, and global estimates of preterm birth in 2020, with trends from 2010: A systematic analysis","volume":"402","author":"EO Ohuma","year":"2023","journal-title":"Lancet"},{"key":"pone.0351293.ref007","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1097\/AOG.0000000000004612","article-title":"Prediction and prevention of spontaneous preterm birth: ACOG practice bulletin, Number 234","volume":"138","author":"MK Hoffman","year":"2021","journal-title":"Obstet Gynecol"},{"issue":"2","key":"pone.0351293.ref008","doi-asserted-by":"crossref","first-page":"369","DOI":"10.3390\/ijerph15020369","article-title":"Different risk factors for very low birth weight, term-small-for-gestational-age, or preterm birth in Japan","volume":"15","author":"N Tamura","year":"2018","journal-title":"Int J Environ Res Public Health"},{"key":"pone.0351293.ref009"},{"key":"pone.0351293.ref010"},{"issue":"2","key":"pone.0351293.ref011","article-title":"Betamimetics for inhibiting preterm labour","volume":"2014","author":"JP Neilson","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"pone.0351293.ref012","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1515\/jpm-2022-0572","article-title":"Maintenance tocolysis, tocolysis in preterm premature rupture of membranes and in cervical cerclage - a Germany-wide survey on the current practice after dissemination of the German guideline","volume":"51","author":"P Stelzl","year":"2023","journal-title":"J Perinat Med"},{"issue":"1","key":"pone.0351293.ref013","first-page":"47","article-title":"Differences between current clinical practice and evidence-based guideline recommendations regarding tocolysis - An austria-wide survey","volume":"85","author":"S Enengl","year":"2024","journal-title":"Geburtshilfe Frauenheilkd"},{"issue":"1","key":"pone.0351293.ref014","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1186\/s12884-018-2078-5","article-title":"Differences between evidence-based recommendations and actual clinical practice regarding tocolysis: A prospective multicenter registry study","volume":"18","author":"E Nazifovic","year":"2018","journal-title":"BMC Pregnancy Childbirth"},{"key":"pone.0351293.ref015","author":"European Medicines Agency"},{"key":"pone.0351293.ref016"},{"issue":"9","key":"pone.0351293.ref017","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1111\/jog.15722","article-title":"Changes in preterm and extremely preterm birth rates in Japan after the introduction of obstetrical practice guidelines in 2008","volume":"49","author":"S Shimano","year":"2023","journal-title":"J Obstet Gynaecol Res"},{"issue":"10","key":"pone.0351293.ref018","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1097\/PCC.0000000000002037","article-title":"Short- and long-term outcomes of extremely preterm infants in Japan according to outborn\/inborn birth status","volume":"20","author":"Y Sasaki","year":"2019","journal-title":"Pediatr Crit Care Med"},{"key":"pone.0351293.ref019"},{"key":"pone.0351293.ref020","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ejogrb.2023.01.011","article-title":"Long-term vs short-term tocolysis with ritodrine hydrochloride: Propensity score-matched analysis","volume":"282","author":"A Okuda","year":"2023","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"pone.0351293.ref021","author":"Ministry of Health, Labour and Welfare"},{"issue":"12","key":"pone.0351293.ref022","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1111\/jog.14484","article-title":"Method to evaluate intravenous maintenance tocolysis for preterm labor","volume":"46","author":"S Yoneda","year":"2020","journal-title":"J Obstet Gynaecol Res"},{"issue":"3","key":"pone.0351293.ref023","first-page":"443","article-title":"Tocolytic therapy inhibiting preterm birth in high-risk populations: A systematic review and meta-analysis","volume":"10","author":"N Yamaji","year":"2023","journal-title":"Children (Basel)"},{"issue":"1","key":"pone.0351293.ref024","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s12931-017-0552-7","article-title":"Outcomes after early and delayed rehabilitation for exacerbation of chronic obstructive pulmonary disease: A nationwide retrospective cohort study in Japan","volume":"18","author":"H Matsui","year":"2017","journal-title":"Respir Res"},{"issue":"1","key":"pone.0351293.ref025","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2188\/jea.JE20200288","article-title":"History and profile of diagnosis procedure combination (DPC): Development of a real data collection system for acute inpatient care in Japan","volume":"31","author":"K Hayashida","year":"2021","journal-title":"J Epidemiol"},{"issue":"4","key":"pone.0351293.ref026","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1136\/bmjqs-2023-016865","article-title":"Factors associated with proximal femoral fractures in older adults during hospital stay: A cross-sectional study","volume":"34","author":"M Moriwaki","year":"2025","journal-title":"BMJ Qual Saf"},{"key":"pone.0351293.ref027","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1007\/s00774-022-01336-4","article-title":"Fractures within 2 years of an obstetric hospitalization: Analysis of nationwide administrative data in Japan","volume":"40","author":"M Toba","year":"2022","journal-title":"J Bone Miner Metab"},{"issue":"4","key":"pone.0351293.ref028","doi-asserted-by":"crossref","first-page":"100822","DOI":"10.1016\/j.identj.2025.04.003","article-title":"Oral management improves patient outcomes in hematopoietic stem cell transplantation","volume":"75","author":"M Moriwaki","year":"2025","journal-title":"Int Dent J"},{"issue":"6","key":"pone.0351293.ref029","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1093\/aje\/kwq433","article-title":"Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries","volume":"173","author":"H Quan","year":"2011","journal-title":"Am J Epidemiol"},{"issue":"5","key":"pone.0351293.ref030","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation","volume":"40","author":"ME Charlson","year":"1987","journal-title":"J Chronic Dis"},{"issue":"4","key":"pone.0351293.ref031","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/1471-0528.16039","article-title":"Do obstetricians apply the national guidelines? A vignette-based study assessing practices for the prevention of preterm birth","volume":"127","author":"A Rousseau","year":"2020","journal-title":"BJOG"},{"issue":"7","key":"pone.0351293.ref032","doi-asserted-by":"crossref","first-page":"4222","DOI":"10.3390\/ijerph19074222","article-title":"Tocolytic treatment for the prevention of preterm birth from a taiwanese perspective: A survey of taiwanese obstetric specialists","volume":"19","author":"HH Lee","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"pone.0351293.ref033","doi-asserted-by":"crossref","first-page":"1030443","DOI":"10.3389\/fgwh.2023.1030443","article-title":"Consolidation of the perinatal care system and workload of obstetricians: An ecological study in Japan","volume":"4","author":"S Hattori","year":"2023","journal-title":"Front Glob Womens Health"},{"issue":"3","key":"pone.0351293.ref034","doi-asserted-by":"crossref","first-page":"100366","DOI":"10.1016\/j.xagr.2024.100366","article-title":"Regional disparities in primary cesarean delivery rates in Japan: The role of obstetrician availability","volume":"4","author":"A Ueda","year":"2024","journal-title":"AJOG Glob Rep"},{"issue":"3","key":"pone.0351293.ref035","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1111\/jog.15543","article-title":"Relationship between out-of-facility deliveries and distance and travel time to delivery facilities in Hokkaido, Japan: An ecological study","volume":"49","author":"Y Saito","year":"2023","journal-title":"J Obstet Gynaecol Res"},{"key":"pone.0351293.ref036"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0351293","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T17:22:15Z","timestamp":1782148935000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0351293"}},"subtitle":[],"editor":[{"given":"Alireza Abdollah","family":"Shamshirsaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,22]]},"references-count":36,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0351293","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,22]]}}}