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      Effectiveness and Safety of Oral Propranolol versus Other Treatments for Infantile Hemangiomas: A Meta-Analysis

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      1 , 2 , * , 1 , 3 , * , 2
      PLoS ONE
      Public Library of Science

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          Abstract

          Background

          Epidemiological studies evaluating treatments for infantile hemangiomas have produced inconsistent results. A meta-analysis of published data was conducted to investigate the effectiveness and safety of oral propranolol versus other treatments for infantile hemangiomas.

          Methods

          A meta-analysis was conducted based on literature (published from 1960 to December 1, 2014) found on the PubMed, EMBASE, and OVID search engines. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for the outcome measures. Heterogeneity, publication bias and subgroup analysis were performed.

          Results

          A total of 61 studies involving 5,130 participants met the inclusion criteria. Propranolol was found to be a more effective modality in treating IHs (ORs = 0.92; 95%CI, 0.89–0.95) and had fewer complications compared to the other treatments including systemic steroids (ORs = 0.68; 95% CI, 0.59–0.76); laser ablation (ORs = 0.55; 95% CI, 0.43–0.67); other beta-adrenergic blockers (ORs = 0.56; 95% CI, 0.50–0.61) and surgery (ORs = 0.55; 95% CI, 0.28–0.81). A subgroup analysis of propranolol showed that a dose of 2 mg/kg/day or more yielded better outcomes (ORs = 0.92; 95% CI, 0.88–0.95; ORs = 0.95; 95% CI, 0.89–1.00), and IHs that had not been previously treated had better responses to propranolol treatment (ORs = 0.95; 95% CI, 0.91–0.98).

          Conclusions

          The meta-analysis demonstrated that propranolol was more effective and safer than other therapies in treating IHs. It provides strong evidence for supporting the use of propranolol as a first-line therapy for IHs.

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          Most cited references63

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          A randomized, controlled trial of oral propranolol in infantile hemangioma.

          Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited.
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            A randomized controlled trial of propranolol for infantile hemangiomas.

            Propranolol hydrochloride is a safe and effective medication for treating infantile hemangiomas (IHs), with decreases in IH volume, color, and elevation. Forty children between the ages of 9 weeks and 5 years with facial IHs or IHs in sites with the potential for disfigurement were randomly assigned to receive propranolol or placebo oral solution 2 mg/kg per day divided 3 times daily for 6 months. Baseline electrocardiogram, echocardiogram, and laboratory evaluations were performed. Monitoring of heart rate, blood pressure, and blood glucose was performed at each visit. Children younger than 6 months were admitted to the hospital for monitoring after their first dose at weeks 1 and 2. Efficacy was assessed by performing blinded volume measurements at weeks 0, 4, 8, 12, 16, 20, and 24 and blinded investigator scoring of photographs at weeks 0, 12, and 24. IH growth stopped by week 4 in the propranolol group. Significant differences in the percent change in volume were seen between groups, with the largest difference at week 12. Significant decrease in IH redness and elevation occurred in the propranolol group at weeks 12 and 24 (P = .01 and .001, respectively). No significant hypoglycemia, hypotension, or bradycardia occurred. One child discontinued the study because of an upper respiratory tract infection. Other adverse events included bronchiolitis, gastroenteritis, streptococcal infection, cool extremities, dental caries, and sleep disturbance. Propranolol hydrochloride administered orally at 2 mg/kg per day reduced the volume, color, and elevation of focal and segmental IH in infants younger than 6 months and children up to 5 years of age.
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              Infantile hemangiomas: current knowledge, future directions. Proceedings of a research workshop on infantile hemangiomas, April 7-9, 2005, Bethesda, Maryland, USA.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                16 September 2015
                2015
                : 10
                : 9
                : e0138100
                Affiliations
                [1 ]College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
                [2 ]Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
                [3 ]Department of Oral and Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
                Emory University, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JZ XQ. Performed the experiments: XL XQ. Analyzed the data: XL XQ. Contributed reagents/materials/analysis tools: XL XQ LZ. Wrote the paper: XL. Reviewed the manuscript: XL XQ JZ LZ.

                Article
                PONE-D-15-17971
                10.1371/journal.pone.0138100
                4573957
                26375455
                7fe4dcb9-ee85-45d6-8fd3-a27b971d8b34
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 25 April 2015
                : 25 August 2015
                Page count
                Figures: 3, Tables: 4, Pages: 16
                Funding
                This work was supported by National Natural Science Foundation of China (81271163, 81470755).
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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