{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T01:24:05Z","timestamp":1792891445564,"version":"4.5.0"},"reference-count":32,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J Gynecology &amp;amp; Obste"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The choice of tocolytic drugs is one of the most debated aspects of preterm birth management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This network meta\u2010analysis aimed to establish an evidence\u2010based hierarchy for tocolytics used in preterm labor by evaluating their efficacy in delaying delivery, safety, and neonatal outcomes. Advanced metrics were applied, including ranking against average efficacy, minimal clinically important difference, and simultaneous evaluation of multiple outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Search Strategy<\/jats:title>\n                    <jats:p>\n                      A comprehensive search of randomized controlled trials was conducted across databases such as Cochrane, PubMed, Scopus,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      , WHO International Clinical Trials Registry Platform, and European Clinical Trials Register (PROSPERO no. CRD420251006201) from inception to March 15, 2025.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Selection Criteria<\/jats:title>\n                    <jats:p>Randomized trials assessing acute tocolytic therapy for preterm labor (24\u201336\u2009weeks). Seven drug classes and placebo\/no\u2010treatment were analyzed: calcium channel blockers, oxytocin receptor antagonists, magnesium sulfate, COX inhibitors, nitric oxide donors, betamimetics, and combination therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Collection and Analysis<\/jats:title>\n                    <jats:p>Risk of bias and confidence in results were assessed using ROB\u20102 and CINeMA. Network meta\u2010analysis was performed using the netmeta package in R. Treatments were ranked using P\u2010scores, surface under the cumulative ranking curve (SUCRA), minimal clinically important difference and simultaneous ranking on efficacy, maternal adverse effects and neonatal mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Results<\/jats:title>\n                    <jats:p>The analysis included 164 studies (18\u2009802 participants). All tocolytics delayed delivery by 48\u2009h more effectively than placebo, with no significant differences among drugs (low to moderate confidence). Calcium channel blockers ranked highest (SUCRA score: 0.99; ranking score vs. average efficacy: 0.998) and were optimal when combining efficacy and safety (P\u2010score: 0.46). Oxytocin receptor antagonists followed, particularly when accounting for minimal clinically important difference (score\u2009=\u20090.42).<\/jats:p>\n                    <jats:p>For 7\u2010day delay, calcium channel blockers and oxytocin receptor antagonists outperformed magnesium sulfate (odds ratio [OR]\u2009=\u20091.83, 95% confidence interval [CI]: 1.15\u20132.94, and OR\u2009=\u20092.02, 95% CI: 1.17\u20133.4) and betamimetics (OR\u2009=\u20091.26, 95% CI: 1\u20131.61, and OR\u2009=\u20091.39, 95% CI: 1\u20131.88). Oxytocin receptor antagonists ranked highest in multiple outcomes at 7\u2009days, while betamimetics ranked lowest due to adverse maternal effects. Precision of hierarchies ranged from moderate (0.62) to high (0.82).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Calcium channel blockers are the most effective and safest tocolytics for short\u2010term delay, supporting current WHO guidelines. Oxytocin receptor antagonists are also highly effective, especially for prolongation beyond 48\u2009h.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p>PROSPERO registration number CRD420251006201, March 16, 2025.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ijgo.71134","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T07:33:58Z","timestamp":1784705638000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Network meta\u2010analysis of tocolytics in preterm labor: Establishing an evidence\u2010based treatment hierarchy"],"prefix":"10.1002","author":[{"given":"Barbara","family":"Gardella","sequence":"first","affiliation":[{"name":"Department of Clinical, Surgical, Diagnostic and Pediatric Sciences University of Pavia  Pavia Italy"},{"name":"Unit of Obstetrics and Gynecology IRCCS S. Matteo Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8055-5086","authenticated-orcid":false,"given":"Chiara","family":"Cassani","sequence":"additional","affiliation":[{"name":"Department of Clinical, Surgical, Diagnostic and Pediatric Sciences University of Pavia  Pavia Italy"},{"name":"Unit of Obstetrics and Gynecology IRCCS S. Matteo Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittoria","family":"Morteo","sequence":"additional","affiliation":[{"name":"Department of Clinical, Surgical, Diagnostic and Pediatric Sciences University of Pavia  Pavia Italy"},{"name":"Unit of Obstetrics and Gynecology IRCCS S. Matteo Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Marmiroli","sequence":"additional","affiliation":[{"name":"Department of Clinical, Surgical, Diagnostic and Pediatric Sciences University of Pavia  Pavia Italy"},{"name":"Unit of Obstetrics and Gynecology IRCCS S. Matteo Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Dominoni","sequence":"additional","affiliation":[{"name":"Department of Clinical, Surgical, Diagnostic and Pediatric Sciences University of Pavia  Pavia Italy"},{"name":"Unit of Obstetrics and Gynecology IRCCS S. Matteo Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arsenio","family":"Spinillo","sequence":"additional","affiliation":[{"name":"Department of Clinical, Surgical, Diagnostic and Pediatric Sciences University of Pavia  Pavia Italy"},{"name":"Unit of Obstetrics and Gynecology IRCCS S. Matteo Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736[23]00878-4"},{"key":"e_1_2_10_2_2","doi-asserted-by":"crossref","unstructured":"Erratum in: Lancet 2024 403 10427:618. doi:10.1016\/S0140\u20106736[24]00267\u20108","DOI":"10.1016\/S0140-6736(24)00237-X"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0029-7844[03]00395-8"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2024.05.006"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/OGX.0000000000001182"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12884-018-2078-5"},{"issue":"2","key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.18203\/2320-1770.ijrcog20240024","article-title":"Role of isoxsuprine as a tocolytic agent in the management of preterm labor in Indian clinical practice","volume":"13","author":"Coelho K","year":"2024","journal-title":"Int J Reprod Contracept Obstet Gynecol"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736[14]60580-8"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD014978.pub2"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X[22]00434-X"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v106.i02"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-021-01488-3"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1463"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/bimj.201900026"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/03635465211053869"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003583"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cl2.1080"},{"key":"e_1_2_10_19_1","unstructured":"\u201cR version 4.4.1 [2024\u201006\u201014 ucrt] \u2013 Race for your life Copyright [C] 2024 The R foundation for statistical computing.\u201d"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2016.02.016"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1002\/jrsm.1373","article-title":"MetaInsight: an interactive web\u2010based tool for analyzing, interrogating, and visualizing network meta\u2010analyses using R\u2010shiny and netmeta","volume":"10","author":"Owen RK","year":"2019","journal-title":"Res Synth Methods"},{"key":"e_1_2_10_22_1","unstructured":"WigleA B\u00e9liveauA SalantiG et\u00a0al.\u201cPrecision of treatment hierarchy: a metric for quantifying certainty in treatment hierarchies from network meta\u2010analysis.\u201darXiv:2501.11596v1.10.48550\/arXiv.2501.11596"},{"key":"e_1_2_10_23_1","unstructured":"EvrenoglouT NikolakopoulouA SchwarzerG R\u00fcckerG ChaimaniA.\u201cProducing treatment hierarchies in network meta\u2010analysis using probabilistic models and treatment\u2010choice criteria.\u201darXiv:2406.10612.10.48550\/arXiv.2406.10612"},{"key":"e_1_2_10_24_1","volume-title":"Statistical Power Analysis for the Behavioral Sciences","author":"Cohen J","year":"1988"},{"key":"e_1_2_10_25_1","volume-title":"Cochrane handbook for systematic reviews of interventions version 6.5","author":"Higgins JPT","year":"2024"},{"key":"e_1_2_10_26_1","first-page":"1161","article-title":"Gauging the safety and efficacy of nytroglicerine used transdermally as a tocolytic agent in females with preterm labor","volume":"16","author":"Ray a","year":"2023","journal-title":"J Cardiovasc Dis Res"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e6226"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.13641"},{"key":"e_1_2_10_29_1","unstructured":"WHO.\u201cWHO recommendation on tocolytic therapy for improving preterm birth outcomes.\u201dWeb Annex. 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