{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T19:51:33Z","timestamp":1793821893746,"version":"4.6.1"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Certain types of fetal cardiac rhabdomyomas can lead to severe complications, including intrauterine death, yet no specific criteria have been established for the prenatal use of pharmacological therapies to mitigate the impact of rhabdomyomas. We conducted a narrative review of case reports and case series published between January 1, 2000, and February 28, 2025, identified through PubMed, Scopus, Web of Science, and Google Scholar, describing the prenatal use of mammalian target of rapamycin inhibitors in this context. Thirteen studies reporting on 15 fetuses were included. Five fetuses (33.3%) had a single rhabdomyoma, and 10 (66.6%) had multiple lesions. Prenatal genetic testing for Tuberous Sclerosis Complex was performed in 9 cases (60%): 1 with a TSC1 mutation, 7 with TSC2 mutations, and 1 negative. Sirolimus was the most frequently used inhibitor (86.6%), while everolimus was used in 2 cases (13.3%). The main indication for treatment was progressive tumor growth causing outflow obstruction and\/or hemodynamic compromise, including reduced cardiac output, arrhythmias, and fetal hydrops. Therapy was initiated at a median of 30.0\u202fweeks (IQR 26.7\u201333.1) and completed at 38.0\u202fweeks (IQR 36\u201339). All reports documented tumor reduction and improved cardiac function, though regrowth occurred in 5 cases (33.3%) after discontinuation. No fetal or neonatal deaths were reported, and none required postnatal cardiac surgery before discharge. Based on these findings, we proposed echocardiographic criteria to identify suitable candidates, including inflow\/outflow tract obstruction, severe atrioventricular valve insufficiency, tachyarrhythmia, impaired cardiac function, or hydrops, and developed a structured prenatal management algorithm. Prenatal therapy with mTOR inhibitors, therefore, appears to improve fetal cardiac function by reducing tumor burden and may contribute to better perinatal outcomes, although validation in future studies is required. TSC1: urn:lsid:hgnc.org: HGNC:12362<\/jats:p>\n                  <jats:p>TSC2: urn:lsid:hgnc.org: HGNC:12363 Sirolimus: urn:lsid:ebi.ac.uk:chebi:9168 Everolimus: urn:lsid:ebi.ac.uk:chebi:68478.<\/jats:p>","DOI":"10.3389\/fmed.2025.1711774","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T06:30:08Z","timestamp":1765175408000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Fetal cardiac rhabdomyomas susceptible to prenatal treatment with mTOR inhibitors: literature review and proposal of a prenatal management algorithm"],"prefix":"10.3389","volume":"12","author":[{"given":"Alfonso","family":"Martinez-Garcia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar A.","family":"Tirado-Aguilar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Acevedo-Gallegos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan M.","family":"Gallardo-Gaona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berenice","family":"Velazquez-Torres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose A.","family":"Ramirez-Calvo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dulce M. A.","family":"Camarena-Cabrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Rodriguez-Sibaja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario I.","family":"Lumbreras-Marquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazmin","family":"Copado-Mendoza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1515\/jpm-2016-0311","article-title":"Fetal cardiac tumors: clinical features, management and prognosis","volume":"46","author":"Yuan","year":"2018","journal-title":"J Perinat Med"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1002\/pd.6640","article-title":"Characteristics and outcomes of fetal cardiac rhabdomyoma with or without mTOR inhibitors, a systematic review and meta-analysis","volume":"4","author":"Mustafa","year":"2024","journal-title":"Prenat Diagn"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.pedneo.2016.07.004","article-title":"Fetal primary cardiac tumors during perinatal period","volume":"58","author":"Yuan","year":"2017","journal-title":"Pediatr Neonatol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1002\/jcu.20857","article-title":"Prenatal sonographic diagnosis of tuberous sclerosis complex","volume":"39","author":"Gedikbasi","year":"2011","journal-title":"J Clin Ultrasound"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1002\/pd.2586","article-title":"Prenatal diagnosis and follow-up of 23 cases of cardiac tumors","volume":"30","author":"Niewiadomska-Jarosik","year":"2010","journal-title":"Prenat Diagn"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1002\/pd.5613","article-title":"Fetal cardiac rhabdomyomas treated with maternal sirolimus","volume":"40","author":"Pluym","year":"2020","journal-title":"Prenat Diagn"},{"key":"ref7","first-page":"1443","article-title":"Primary cardiac tumours: eighteen years of surgical experience on 21 patients","volume":"20","author":"Piazza","year":"2004","journal-title":"Can J Cardiol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1067\/S0022-3476(03)00250-6","article-title":"Left ventricular outflow obstruction in rhabdomyoma of infancy: meta-analysis of the literature","volume":"143","author":"Verhaaren","year":"2003","journal-title":"J Pediatr"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1212\/WNL.0b013e3182815428","article-title":"Everolimus long-term safety and efficacy in subependymal giant cell astrocytoma","volume":"80","author":"Krueger","year":"2013","journal-title":"Neurology"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"721","DOI":"10.7164\/antibiotics.28.721","article-title":"Rapamycin (AY-22,989), a new antifungal antibiotic. 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