Interventions for Infantile Haemangiomas of the Skin

Abridged Cochrane Systematic Review and Grade Assessments

M. Novoa; E. Baselga; S. Beltran; L. Giraldo; A. Shahbaz; H. Pardo-Hernandez ID; I. Arevalo-Rodriguez ID


The British Journal of Dermatology. 2019;180(3):527-533. 

In This Article

Abstract and Introduction


Background: Infantile haemangiomas (IH) are soft swellings of the skin that occur in 3–10% of infants. When haemangiomas occur in high-risk areas or when complications develop, active intervention is necessary.

Objective: To update a Cochrane Review assessing the interventions for the management of IH in children.

Methods: We searched for randomized controlled trials in CENTRAL, MEDLINE, Embase, LILACS, AMED, PsycINFO, CINAHL and six trials registers up to February 2017. We included 28 trials (1728 participants) assessing 12 interventions.

Results: We downgraded evidence from high to moderate/low for issues related to risk of bias and imprecision. Oral propranolol (3 mg kg−1 daily) probably improves clinician-assessed clearance vs placebo [risk ratio (RR) 16·61, 95% confidence interval (CI) 4·22–65·34; moderate quality of evidence (QoE)]; we found no evidence of a difference in terms of serious adverse events (RR 1·05, 95% CI 0·33–3·39; low QoE). We found the chance of reduction of redness may be improved with topical timolol maleate (0·5% gel applied twice daily) when compared with placebo (RR 8·11, 95% CI 1·09–60·09; low QoE). We found no instances of bradycardia or hypotension for this comparison.

Conclusions: Our key results indicate that oral propranolol and topical timolol maleate are more beneficial than placebo in terms of clearance or other measures of resolution, or both, without an increase in harm.


Infantile haemangiomas (IH) are the most common vascular tumours in children, occurring in 3–10% of infants.[1,2] They were previously known as 'strawberry birthmarks' or 'strawberry naevi', or 'capillary haemangiomas', terms currently withdrawn by current classifications of vascular tumours.[1] They are benign and of endothelial cellular origin, characterized by a rapid pattern of proliferation in the first months of life, then followed by a period of involution that can take several years.[3]

While the majority of IH are nonproblematic and will regress and disappear in 5–7 years, a few will become problematic or cause psychological distress to children and their parents,[4,5] such as IH in high-risk areas, i.e. near the eyes, throat or nose, impairing their function. Some IH may also result in complications, including congestive heart failure, lifelong disfigurement, bleeding, ulceration and visual and airway-related obstruction.[4] In such cases, intervention with a variety of medical treatments may be necessary. Propranolol therapy has been recommended as the most effective way of treating IH, as it inhibits proliferation and incites regression of IH during the proliferative phase.[2,6–15] However, a large variety of treatments have been used historically, and many are still in use. It was therefore necessary to review the efficacy and potential adverse events of these interventions for the management of IH.[1]

A first assessment of these interventions was published by Leonardi-Bee et al. in 2011,[16] reporting information from four trials with limited evidence. This article is a summary of the updated Cochrane review evaluating potential interventions in the management of IH of the skin.[1]