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We aimed to evaluate the efficacy and safety of propranolol monotherapy versus propranolol plus prednisone for the treatment of problematic IHHs to determine whether oral prednisone provided an added benefit to propranolol.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted an open-label, multicenter, randomized controlled trial across six referral centers in China from July 2019 to November 2023 (clinicaltrials.gov registration: NCT03331744). Infants with problematic diffuse IHH were assigned (1:1) to oral propranolol alone or propranolol plus a short course of prednisone. The primary endpoint was the proportion of patients who achieved a lesion response at week 4 on serial ultrasound. Analyses followed the intention-to-treat principle.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Forty-five patients were included in this study (propranolol,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200922; propranolol plus prednisone,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200923). Four weeks following treatment, lesion response rates were higher with propranolol plus prednisone than with propranolol alone [21\/23 (91.3%) vs. 13\/22 (59.1%); difference: 32.2%; 95% confidence interval (CI)\u2009=\u20096.9%\u201353.5%;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.007]. Compared with monotherapy, combination therapy yielded higher lesion response rates during weeks 1\u20133, more rapid stabilization of thyroid-stimulating hormone levels during weeks 2\u20134, and a greater overall volumetric response at month 6 (91.3% vs. 63.6%; difference: 27.7%; 95% CI\u2009=\u20093.1%\u201349.3%;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.026). Total adverse events were similar between the groups, and no grade 3\u20134 adverse events were observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Addition of prednisone to propranolol in patients with diffuse IHH markedly improved lesion response rates. Propranolol plus prednisone represents a valid treatment for diffuse IHH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12519-026-01070-1","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T17:18:23Z","timestamp":1784049503000},"page":"655-663","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Propranolol monotherapy versus propranolol plus prednisone for diffuse infantile hepatic haemangioma: a randomized clinical trial"],"prefix":"10.1007","volume":"22","author":[{"given":"Yu-Ru","family":"Lan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Xin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin-Yu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Zhi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang-Yuan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Peng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Shui","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping-Qian","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Chao","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Yuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9289-9660","authenticated-orcid":false,"given":"Yi","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"1070_CR1","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.jpedsurg.2008.10.021","volume":"44","author":"B Dickie","year":"2009","unstructured":"Dickie B, Dasgupta R, Nair R, Alonso MH, Ryckman FC, Tiao GM, et al. 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The trial was performed in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from the parents\/guardians of all patients included. This trial is registered with\n                      \n                      under the identifier of NCT03331744.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}