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

Materials and Methods

We updated a previously published review, following methods approved by Cochrane.[1,17]

Search Strategies

We searched the Cochrane Skin Group Specialised Skin Register; CENTRAL (2017, Issue 1); MEDLINE (from 1946); Embase (from 1974); LILACS (from 1982); AMED (from 1985); PsycINFO (from 1806); CINAHL (from 1981); and five trials registers. Then we checked the reference lists of the included studies for additional trials (Appendix S1; see Supporting Information). The last search was conducted in February 2017. Two authors independently carried out study selection, and disagreements were resolved by discussion.

Inclusion Criteria

We included randomized controlled trials evaluating any interventions for the management of IH in children with single or multiple lesions located on the skin. We excluded children with cases of very rare types of haemangioma (including congenital haemangioma, haemangiomas associated with Kasabach–Merritt syndrome, and eruptive neonatal haemangiomatosis) and internal haemangiomas. We considered all interventions alone or in combination vs. 'wait and see', placebo or other interventions.

Outcome Measures

The primary outcomes were: (i) clearance (proportion of children with lesions completely cleared or with minimal residual signs), as assessed by a clinician at any follow-up; (ii) a subjective measure of improvement, as assessed by the parent or child, at any follow-up; and (iii) adverse events experienced in the short or long term related to each intervention.

The secondary outcomes were: (i) other measures of resolution (i.e. surface area, height or volume of lesion, and redness of lesion), as assessed by a clinician, at any follow-up; (ii) proportion of parents who consider their child still has a problem, at any follow-up; (iii) proportion of children who consider they still have a problem, at any follow-up; (iv) aesthetic appearance as assessed by physician, child, or parent, at any follow-up; and (v) requirement for surgical correction, as assessed by a physician, at any follow-up.

Data Extraction and Synthesis

Two authors independently performed data extraction and assessed the risk of bias of included studies.[17] We took six domains into consideration: random sequence generation; blinding of participants and personnel; blinding of outcome assessment; allocation concealment; selective reporting; and other biases. Other biases, such as interim results, contamination, or inappropriate influence of funders, were assessed as outlined in the Cochrane Handbook for Systematic Reviews of Interventions.[17] We judged each domain to be at low, high or unclear risk of bias. Risk ratios (RRs) were calculated for dichotomous outcomes and mean differences for continuous outcomes; they were reported with their corresponding 95% confidence intervals (CIs). We investigated heterogeneity with close visual examination of the forest plots and by means of the I2 statistic.[17] The I2 statistic is employed to describe the percentage total variation across all contributing trials due to heterogeneity rather than sampling error. If we identified signs of heterogeneity (I2 > 30%), we performed further exploration by prespecified subgroup analysis; furthermore, if we identified considerable percentage of heterogeneity (I2 > 80%), we did not present pooled results.[17] We assessed the quality of the body of evidence (also known as certainty in the evidence) pertaining to primary and secondary outcomes using the principles of the GRADE approach.[18]