{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T21:10:37Z","timestamp":1769029837547,"version":"3.49.0"},"reference-count":22,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003123","name":"Fetal Medicine Foundation","doi-asserted-by":"crossref","award":["1037116"],"award-info":[{"award-number":["1037116"]}],"id":[{"id":"10.13039\/501100003123","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Gestational diabetes mellitus (GDM) is associated with metabolic disturbance and subclinical cardiovascular changes during pregnancy and after birth. Optimal glycaemic control remains challenging for many patients despite existing management strategies. Ursodeoxycholic acid (UDCA) has shown potential metabolic effects, including enhanced insulin sensitivity and anti-inflammatory effects. Previously, we demonstrated that UDCA improves glycaemic control in women achieving higher circulating UDCA concentrations; however, its effect on maternal cardiac function remains unknown. The objective was to evaluate whether treatment with UDCA compared with placebo is associated with differences in maternal cardiac function in pregnancies complicated by GDM. Methods: In this randomized, placebo-controlled trial, 113 women with GDM were recruited, with 56 allocated to UDCA and 57 to placebo (IMIB-GU-2019-02, registration date: 17 June 2020; first participant enrolled: 3 March 2021). After measurement of maternal blood UDCA levels, 43 participants in the treatment group with levels \u2265 0.5 \u03bcmol\/L were included in a per-protocol analysis. Participants had cardiac assessments at baseline, in the late third trimester (36 weeks) and postpartum. Detailed left ventricular systolic and diastolic functional indices were assessed using conventional pulse and tissue Doppler indices as well as strain imaging. Right ventricular systolic function was also assessed. Results: Baseline maternal characteristics and cardiac functional indices were comparable between the UDCA and placebo groups. In the third trimester, women treated with UDCA showed more negative left atrial strain during atrial contraction (LASct_AC) compared with placebo (p = 0.016), while no significant between-group differences were observed in conventional left ventricular systolic or diastolic parameters. In the postpartum period, UDCA treatment was associated with higher left atrial reservoir function, reflected by increased LASr_ED (p = 0.041) and LASr_AC (p = 0.036), as well as more negative left atrial conduit strain at end-diastole (LAScd_ED; p = 0.043). No consistent differences were observed in left ventricular systolic function, haemodynamic indices, or right ventricular functional parameters between the two groups. Conclusions: These findings are associated with small and time-dependent differences in reducing atrial dysfunction and improving cardiac efficiency during late pregnancy and postpartum. However, given the lack of long-term follow-up, further research is needed to determine the long-term cardiovascular relevance of UDCA in this population.<\/jats:p>","DOI":"10.3390\/jcm15020786","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T09:24:34Z","timestamp":1768901074000},"page":"786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Impact of Ursodeoxycholic Acid on Maternal Cardiac Function in Women with Gestational Diabetes Mellitus: A Randomized Controlled Study (GUARDS Trial)"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3653-4069","authenticated-orcid":false,"given":"Ana Mar\u00eda Company","family":"Calabuig","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, El Palmar, 30120 Murcia, Spain"},{"name":"Faculty of Medicine, Universidad de Murcia, 30107 Murcia, Spain"},{"name":"Biomedical Research Institute of Murcia Pascual Parrilla\u2014IMIB, 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0511-3533","authenticated-orcid":false,"given":"Jose Eliseo","family":"Blanco-Carnero","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, El Palmar, 30120 Murcia, Spain"},{"name":"Faculty of Medicine, Universidad de Murcia, 30107 Murcia, Spain"},{"name":"Biomedical Research Institute of Murcia Pascual Parrilla\u2014IMIB, 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5895-6887","authenticated-orcid":false,"given":"Christos","family":"Chatzakis","sequence":"additional","affiliation":[{"name":"Harris Birthright Research Centre for Fetal Medicine, King\u2019s College, London SE5 8BB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6226-7611","authenticated-orcid":false,"given":"Catherine","family":"Williamson","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion & Reproduction, Imperial College London, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kypros H.","family":"Nicolaides","sequence":"additional","affiliation":[{"name":"Harris Birthright Research Centre for Fetal Medicine, King\u2019s College, London SE5 8BB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catalina","family":"De Paco Matallana","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, El Palmar, 30120 Murcia, Spain"},{"name":"Faculty of Medicine, Universidad de Murcia, 30107 Murcia, Spain"},{"name":"Biomedical Research Institute of Murcia Pascual Parrilla\u2014IMIB, 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marietta","family":"Charakida","sequence":"additional","affiliation":[{"name":"Harris Birthright Research Centre for Fetal Medicine, King\u2019s College, London SE5 8BB, UK"},{"name":"School of Biomedical Engineering and Imaging Sciences, King\u2019s College London, London SE1 7EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/S0140-6736(09)60731-5","article-title":"Type 2 diabetes mellitus after gestational diabetes: A systematic review and meta-analysis","volume":"373","author":"Bellamy","year":"2009","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.2337\/diacare.25.10.1862","article-title":"Gestational diabetes and the incidence of type 2 diabetes: A systematic review","volume":"25","author":"Kim","year":"2002","journal-title":"Diabetes Care"},{"key":"ref_3","first-page":"e018951","article-title":"History of gestational diabetes mellitus and future risk of atherosclerosis in midlife: The CARDIA study","volume":"10","author":"Gunderson","year":"2021","journal-title":"J. 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