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Intervenciones para los hemangiomas infantiles cutáneos

Appendices

Appendix 1. Skin Group Specialised Register (CRS) search strategy

#1 MeSH DESCRIPTOR Hemangioma
#2 MeSH DESCRIPTOR Hemangioma, Capillary
#3 MeSH DESCRIPTOR Hemangioma, Cavernous
#4 (hemangioma* or haemangioma*)
#5 (capillary and (naev* or nev*))
#6 (strawberry and (naev* or nev*))
#7 (strawberry birthmark*)
#8 (strawberry mark*)
#9 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8

Appendix 2. CENTRAL (Cochrane Library) search strategy

#1 hemangioma* or haemangioma*:ti,ab,kw
#2 MeSH descriptor: [Hemangioma] explode all trees
#3 MeSH descriptor: [Hemangioma, Capillary] explode all trees
#4 capillary and (naev* or nev*):ti,ab,kw
#5 strawberry and (naev* or nev*):ti,ab,kw
#6 strawberry birthmark*:ti,ab,kw
#7 MeSH descriptor: [Hemangioma, Cavernous] explode all trees
#8 strawberry mark*:ti,ab,kw
#9 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8

Appendix 3. MEDLINE (Ovid) search strategy

1. exp Hemangioma, Capillary/ or exp Hemangioma/ or exp Hemangioma, Cavernous/
2. (haemangioma$ or hemangioma$).mp.
3. (strawberry naev$ or strawberry nev$).mp.
4. (capillary naev$ or capillary nev$).mp.
5. (superficial angiomatous naev$ or superficial angiomatous nev$).mp.
6. strawberry birthmark$.mp.
7. strawberry mark$.mp.
8. 1 or 2 or 3 or 4 or 5 or 6 or 7
9. randomized controlled trial.pt.
10. controlled clinical trial.pt.
11. randomized.ab.
12. placebo.ab.
13. clinical trials as topic.sh.
14. randomly.ab.
15. trial.ti.
16. 9 or 10 or 11 or 12 or 13 or 14 or 15
17. exp animals/ not humans.sh.
18. 16 not 17
19. 8 and 18

Lines 9‐18: Cochrane Highly Sensitive Search Strategy for identifying randomized trials in MEDLINE: sensitivity‐ and precision‐maximizing version (2008 revision).

Appendix 4. Embase (Ovid) search strategy

1. exp skin hemangioma/ or exp capillary hemangioma/ or exp hemangioma/ or exp cavernous hemangioma/
2. (haemangioma$ or hemangioma$).mp.
3. (strawberry naev$ or strawberry nev$).mp.
4. (capillary naev$ or capillary nev$).mp.
5. (superficial angiomatous naev$ or superficial angiomatous nev$).mp.
6. strawberry birthmark$.mp.
7. strawberry mark$.mp.
8. or/1‐7
9. crossover procedure.sh.
10. double‐blind procedure.sh.
11. single‐blind procedure.sh.
12. (crossover$ or cross over$).tw.
13. placebo$.tw.
14. (doubl$ adj blind$).tw.
15. allocat$.tw.
16. trial.ti.
17. randomized controlled trial.sh.
18. random$.tw.
19. or/9‐18
20. exp animal/ or exp invertebrate/ or animal experiment/ or animal model/ or animal tissue/ or animal cell/ or nonhuman/
21. human/ or normal human/
22. 20 and 21
23. 20 not 22
24. 19 not 23
25. 8 and 24

Appendix 5. AMED (Ovid) search strategy

1. (haemangioma$ or hemangioma$).mp.
2. strawberry birthmark$.mp.
3. strawberry mark$.mp.
4. or/1‐3
5. randomized controlled trial$/
6. random allocation/
7. double blind method/
8. single blind method.mp.
9. exp Clinical trials/
10. (clin$ adj25 trial$).mp.
11. ((singl$ or doubl$ or trebl$ or tripl$) adj25 (blind$ or mask$ or dummy)).mp.
12. (placebo$ or random$).mp.
13. research design/ or clinical trials/ or comparative study/ or double blind method/ or random allocation/
14. prospective studies.mp.
15. cross over studies.mp.
16. Follow up studies/
17. control$.mp.
18. (multicent$ or multi‐cent$).mp.
19. ((stud or design$) adj25 (factorial or prospective or intervention or crossver or cross‐over or quasi‐experiment$)).mp.
20. 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19
21. 4 and 20

Appendix 6. PsycINFO (Ovid) search strategy

1. (haemangioma$ or hemangioma$).mp.
2. strawberry birthmark$.mp.
3. strawberry mark$.mp.
4. or/1‐3
5. double‐blind.tw.
6. random$ assigned.tw.
7. control.tw.
8. 5 or 6 or 7
9. 4 and 8

Lines 5‐8: therapy filter for PsycINFO (Ovid) created by the Health Information Research Unit at McMaster University.

Appendix 7. LILACS search strategy

In LILACS we searched using the Controlled clinical trials topic‐specific query filter and the following terms: hemangioma$ or haemangioma$ or nevi or nevus

Appendix 8. CINAHL (EBSCO) search strategy

S1 TX strawberry birthmark*
S2 TX strawberry mark*
S3 (MM "Hemangioma+") OR (MM "Hemangioma, Cavernous")
S4 (MH "Clinical Trials+")
S5 PT clinical trial
S6 TX (clinic* n1 trial*)
S7 (MH "Random Assignment")
S8 TX random* allocat*
S9 TX placebo*
S10 (MH "Placebos")
S11 (MH "Quantitative Studies")
S12 TX allocat* random*
S13 "randomi#ed control* trial*"
S14 TX ( (singl* n1 blind*) or (singl* n1 mask*) ) or TX ( (doubl* n1 blind*) or (doubl* n1 mask*) ) or TX ( (tripl* n1 blind*) or (tripl* n1 mask*) ) or TX ( (trebl* n1 blind*) or (trebl* n1 mask*) )
S15 S4 or S5 or S6 or S7 or S8 or S9 or S10 or S11 or S12 or S13 or S14
S16 TI ( haemangioma* or hemangioma* ) OR AB ( haemangioma* or hemangioma* )
S17 S1 OR S2 OR S3 OR S16
S18 S15 AND S17

Lines S4 to S15: based on the SIGN filter for RCTs in CINAHL via EBSCO.

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies.
Figures and Tables -
Figure 2

'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies.

'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study.
Figures and Tables -
Figure 3

'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study.

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 1 Clearance.
Figures and Tables -
Analysis 1.1

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 1 Clearance.

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 2 Adverse events: skin atrophy.
Figures and Tables -
Analysis 1.2

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 2 Adverse events: skin atrophy.

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 3 Adverse events: skin hypopigmentation.
Figures and Tables -
Analysis 1.3

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 3 Adverse events: skin hypopigmentation.

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 4 Adverse events: minimal crusting.
Figures and Tables -
Analysis 1.4

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 4 Adverse events: minimal crusting.

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 5 Adverse events: pain.
Figures and Tables -
Analysis 1.5

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 5 Adverse events: pain.

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 6 Other measures of resolution: no redness.
Figures and Tables -
Analysis 1.6

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 6 Other measures of resolution: no redness.

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 7 Parents who consider that their child still has a problem.
Figures and Tables -
Analysis 1.7

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 7 Parents who consider that their child still has a problem.

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 8 Aesthetic appearance: better cosmetic outcome.
Figures and Tables -
Analysis 1.8

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 8 Aesthetic appearance: better cosmetic outcome.

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 9 Requirement for surgical correction.
Figures and Tables -
Analysis 1.9

Comparison 1 Pulsed dye laser versus wait‐and‐see, Outcome 9 Requirement for surgical correction.

Comparison 2 Oral propranolol versus placebo, Outcome 1 Clearance, as assessed by a clinician.
Figures and Tables -
Analysis 2.1

Comparison 2 Oral propranolol versus placebo, Outcome 1 Clearance, as assessed by a clinician.

Comparison 2 Oral propranolol versus placebo, Outcome 2 Serious adverse events.
Figures and Tables -
Analysis 2.2

Comparison 2 Oral propranolol versus placebo, Outcome 2 Serious adverse events.

Comparison 2 Oral propranolol versus placebo, Outcome 3 Serious cardiovascular adverse events.
Figures and Tables -
Analysis 2.3

Comparison 2 Oral propranolol versus placebo, Outcome 3 Serious cardiovascular adverse events.

Comparison 2 Oral propranolol versus placebo, Outcome 4 Other adverse events.
Figures and Tables -
Analysis 2.4

Comparison 2 Oral propranolol versus placebo, Outcome 4 Other adverse events.

Comparison 2 Oral propranolol versus placebo, Outcome 5 Other measures of resolution: change in volume.
Figures and Tables -
Analysis 2.5

Comparison 2 Oral propranolol versus placebo, Outcome 5 Other measures of resolution: change in volume.

Comparison 2 Oral propranolol versus placebo, Outcome 6 Other measures of resolution: no improvement in redness.
Figures and Tables -
Analysis 2.6

Comparison 2 Oral propranolol versus placebo, Outcome 6 Other measures of resolution: no improvement in redness.

Comparison 3 Topical timolol maleate versus placebo, Outcome 1 Other measures of resolution (6 months).
Figures and Tables -
Analysis 3.1

Comparison 3 Topical timolol maleate versus placebo, Outcome 1 Other measures of resolution (6 months).

Comparison 4 Topical bleomycin versus placebo, Outcome 1 Other measures of resolution: reduction in size at day 7.
Figures and Tables -
Analysis 4.1

Comparison 4 Topical bleomycin versus placebo, Outcome 1 Other measures of resolution: reduction in size at day 7.

Comparison 5 X‐ray radiation versus sham radiation, Outcome 1 Clearance.
Figures and Tables -
Analysis 5.1

Comparison 5 X‐ray radiation versus sham radiation, Outcome 1 Clearance.

Comparison 6 Topical timolol maleate versus Nd:YAG laser, Outcome 1 Other measures of resolution (continuous).
Figures and Tables -
Analysis 6.1

Comparison 6 Topical timolol maleate versus Nd:YAG laser, Outcome 1 Other measures of resolution (continuous).

Comparison 6 Topical timolol maleate versus Nd:YAG laser, Outcome 2 Other measures of resolution (dichotomous).
Figures and Tables -
Analysis 6.2

Comparison 6 Topical timolol maleate versus Nd:YAG laser, Outcome 2 Other measures of resolution (dichotomous).

Comparison 7 Nd:YAG laser versus oral propranolol, Outcome 1 Clearance.
Figures and Tables -
Analysis 7.1

Comparison 7 Nd:YAG laser versus oral propranolol, Outcome 1 Clearance.

Comparison 7 Nd:YAG laser versus oral propranolol, Outcome 2 Adverse events: hyperpigmentation.
Figures and Tables -
Analysis 7.2

Comparison 7 Nd:YAG laser versus oral propranolol, Outcome 2 Adverse events: hyperpigmentation.

Comparison 7 Nd:YAG laser versus oral propranolol, Outcome 3 Adverse event: pigmentation and thinning.
Figures and Tables -
Analysis 7.3

Comparison 7 Nd:YAG laser versus oral propranolol, Outcome 3 Adverse event: pigmentation and thinning.

Comparison 7 Nd:YAG laser versus oral propranolol, Outcome 4 Adverse events: superficial scar.
Figures and Tables -
Analysis 7.4

Comparison 7 Nd:YAG laser versus oral propranolol, Outcome 4 Adverse events: superficial scar.

Comparison 7 Nd:YAG laser versus oral propranolol, Outcome 5 Other measures of resolution: excellent response.
Figures and Tables -
Analysis 7.5

Comparison 7 Nd:YAG laser versus oral propranolol, Outcome 5 Other measures of resolution: excellent response.

Comparison 8 Pulsed dye laser + topical propranolol versus pulsed dye laser, Outcome 1 Clearance, as assessed by a clinician.
Figures and Tables -
Analysis 8.1

Comparison 8 Pulsed dye laser + topical propranolol versus pulsed dye laser, Outcome 1 Clearance, as assessed by a clinician.

Comparison 9 Pulsed dye laser + topical timolol maleate versus pulsed dye laser, Outcome 1 Clearance.
Figures and Tables -
Analysis 9.1

Comparison 9 Pulsed dye laser + topical timolol maleate versus pulsed dye laser, Outcome 1 Clearance.

Comparison 9 Pulsed dye laser + topical timolol maleate versus pulsed dye laser, Outcome 2 Other measures of resolution: mean size reduction.
Figures and Tables -
Analysis 9.2

Comparison 9 Pulsed dye laser + topical timolol maleate versus pulsed dye laser, Outcome 2 Other measures of resolution: mean size reduction.

Comparison 10 Nd:YAG laser + oral propranolol versus Nd:YAG laser, Outcome 1 Clearance.
Figures and Tables -
Analysis 10.1

Comparison 10 Nd:YAG laser + oral propranolol versus Nd:YAG laser, Outcome 1 Clearance.

Comparison 10 Nd:YAG laser + oral propranolol versus Nd:YAG laser, Outcome 2 Adverse events: hyperpigmentation.
Figures and Tables -
Analysis 10.2

Comparison 10 Nd:YAG laser + oral propranolol versus Nd:YAG laser, Outcome 2 Adverse events: hyperpigmentation.

Comparison 10 Nd:YAG laser + oral propranolol versus Nd:YAG laser, Outcome 3 Adverse events: pigmentation and thinning.
Figures and Tables -
Analysis 10.3

Comparison 10 Nd:YAG laser + oral propranolol versus Nd:YAG laser, Outcome 3 Adverse events: pigmentation and thinning.

Comparison 10 Nd:YAG laser + oral propranolol versus Nd:YAG laser, Outcome 4 Adverse events: superficial scar.
Figures and Tables -
Analysis 10.4

Comparison 10 Nd:YAG laser + oral propranolol versus Nd:YAG laser, Outcome 4 Adverse events: superficial scar.

Comparison 10 Nd:YAG laser + oral propranolol versus Nd:YAG laser, Outcome 5 Other measures of resolution: excellent response.
Figures and Tables -
Analysis 10.5

Comparison 10 Nd:YAG laser + oral propranolol versus Nd:YAG laser, Outcome 5 Other measures of resolution: excellent response.

Comparison 11 Nd:YAG laser + oral propranolol versus oral propranolol, Outcome 1 Clearance.
Figures and Tables -
Analysis 11.1

Comparison 11 Nd:YAG laser + oral propranolol versus oral propranolol, Outcome 1 Clearance.

Comparison 11 Nd:YAG laser + oral propranolol versus oral propranolol, Outcome 2 Adverse events: hyperpigmentation.
Figures and Tables -
Analysis 11.2

Comparison 11 Nd:YAG laser + oral propranolol versus oral propranolol, Outcome 2 Adverse events: hyperpigmentation.

Comparison 11 Nd:YAG laser + oral propranolol versus oral propranolol, Outcome 3 Adverse events: pigmentation and thinning.
Figures and Tables -
Analysis 11.3

Comparison 11 Nd:YAG laser + oral propranolol versus oral propranolol, Outcome 3 Adverse events: pigmentation and thinning.

Comparison 11 Nd:YAG laser + oral propranolol versus oral propranolol, Outcome 4 Adverse events: superficial scar.
Figures and Tables -
Analysis 11.4

Comparison 11 Nd:YAG laser + oral propranolol versus oral propranolol, Outcome 4 Adverse events: superficial scar.

Comparison 11 Nd:YAG laser + oral propranolol versus oral propranolol, Outcome 5 Other measures of resolution: excellent response.
Figures and Tables -
Analysis 11.5

Comparison 11 Nd:YAG laser + oral propranolol versus oral propranolol, Outcome 5 Other measures of resolution: excellent response.

Comparison 12 ⁹⁰SR‐⁹⁰Y radiation + topical timolol maleate versus ⁹⁰SR‐⁹⁰Y radiation, Outcome 1 Clearance.
Figures and Tables -
Analysis 12.1

Comparison 12 ⁹⁰SR‐⁹⁰Y radiation + topical timolol maleate versus ⁹⁰SR‐⁹⁰Y radiation, Outcome 1 Clearance.

Comparison 12 ⁹⁰SR‐⁹⁰Y radiation + topical timolol maleate versus ⁹⁰SR‐⁹⁰Y radiation, Outcome 2 Adverse events.
Figures and Tables -
Analysis 12.2

Comparison 12 ⁹⁰SR‐⁹⁰Y radiation + topical timolol maleate versus ⁹⁰SR‐⁹⁰Y radiation, Outcome 2 Adverse events.

Comparison 13 Sequential dual‐wavelength laser + oral propranolol versus concurrent dual‐wavelength laser + oral propranolol, Outcome 1 Other outcomes of resolution: mean efficacy rating.
Figures and Tables -
Analysis 13.1

Comparison 13 Sequential dual‐wavelength laser + oral propranolol versus concurrent dual‐wavelength laser + oral propranolol, Outcome 1 Other outcomes of resolution: mean efficacy rating.

Comparison 14 Oral propranolol versus topical propranolol, Outcome 1 Clearance.
Figures and Tables -
Analysis 14.1

Comparison 14 Oral propranolol versus topical propranolol, Outcome 1 Clearance.

Comparison 14 Oral propranolol versus topical propranolol, Outcome 2 Adverse events: syncopal attack.
Figures and Tables -
Analysis 14.2

Comparison 14 Oral propranolol versus topical propranolol, Outcome 2 Adverse events: syncopal attack.

Comparison 15 Oral propranolol versus intralesional propranolol, Outcome 1 Clearance.
Figures and Tables -
Analysis 15.1

Comparison 15 Oral propranolol versus intralesional propranolol, Outcome 1 Clearance.

Comparison 15 Oral propranolol versus intralesional propranolol, Outcome 2 Adverse events: syncopal attack.
Figures and Tables -
Analysis 15.2

Comparison 15 Oral propranolol versus intralesional propranolol, Outcome 2 Adverse events: syncopal attack.

Comparison 16 Topical propranolol versus intralesional propranolol, Outcome 1 Clearance.
Figures and Tables -
Analysis 16.1

Comparison 16 Topical propranolol versus intralesional propranolol, Outcome 1 Clearance.

Comparison 17 Oral atenolol versus oral propranolol, Outcome 1 Clearance.
Figures and Tables -
Analysis 17.1

Comparison 17 Oral atenolol versus oral propranolol, Outcome 1 Clearance.

Comparison 18 Oral propranolol versus oral prednisolone, Outcome 1 Severe adverse events.
Figures and Tables -
Analysis 18.1

Comparison 18 Oral propranolol versus oral prednisolone, Outcome 1 Severe adverse events.

Comparison 18 Oral propranolol versus oral prednisolone, Outcome 2 Adverse events: complications in general.
Figures and Tables -
Analysis 18.2

Comparison 18 Oral propranolol versus oral prednisolone, Outcome 2 Adverse events: complications in general.

Comparison 18 Oral propranolol versus oral prednisolone, Outcome 3 Other measures of resolution: colour fading.
Figures and Tables -
Analysis 18.3

Comparison 18 Oral propranolol versus oral prednisolone, Outcome 3 Other measures of resolution: colour fading.

Comparison 18 Oral propranolol versus oral prednisolone, Outcome 4 Other measures of resolution: mean size reduction.
Figures and Tables -
Analysis 18.4

Comparison 18 Oral propranolol versus oral prednisolone, Outcome 4 Other measures of resolution: mean size reduction.

Comparison 18 Oral propranolol versus oral prednisolone, Outcome 5 Other measures of resolution: proportional change in the total surface area.
Figures and Tables -
Analysis 18.5

Comparison 18 Oral propranolol versus oral prednisolone, Outcome 5 Other measures of resolution: proportional change in the total surface area.

Comparison 19 Oral propranolol versus oral captopril, Outcome 1 Clearance.
Figures and Tables -
Analysis 19.1

Comparison 19 Oral propranolol versus oral captopril, Outcome 1 Clearance.

Comparison 19 Oral propranolol versus oral captopril, Outcome 2 Adverse events: cardiac side effects.
Figures and Tables -
Analysis 19.2

Comparison 19 Oral propranolol versus oral captopril, Outcome 2 Adverse events: cardiac side effects.

Comparison 20 Oral propranolol versus topical timolol maleate, Outcome 1 Adverse events.
Figures and Tables -
Analysis 20.1

Comparison 20 Oral propranolol versus topical timolol maleate, Outcome 1 Adverse events.

Comparison 20 Oral propranolol versus topical timolol maleate, Outcome 2 Other measures of resolution: size reduction > 50%.
Figures and Tables -
Analysis 20.2

Comparison 20 Oral propranolol versus topical timolol maleate, Outcome 2 Other measures of resolution: size reduction > 50%.

Comparison 21 Oral propranolol versus oral propranolol + oral prednisolone, Outcome 1 Adverse events in general.
Figures and Tables -
Analysis 21.1

Comparison 21 Oral propranolol versus oral propranolol + oral prednisolone, Outcome 1 Adverse events in general.

Comparison 21 Oral propranolol versus oral propranolol + oral prednisolone, Outcome 2 Other measures of resolution: mean size reduction.
Figures and Tables -
Analysis 21.2

Comparison 21 Oral propranolol versus oral propranolol + oral prednisolone, Outcome 2 Other measures of resolution: mean size reduction.

Comparison 21 Oral propranolol versus oral propranolol + oral prednisolone, Outcome 3 Other measures of resolution: decrease in redness.
Figures and Tables -
Analysis 21.3

Comparison 21 Oral propranolol versus oral propranolol + oral prednisolone, Outcome 3 Other measures of resolution: decrease in redness.

Comparison 22 Oral propranolol versus oral ibuprofen + oral paracetamol, Outcome 1 Clearance.
Figures and Tables -
Analysis 22.1

Comparison 22 Oral propranolol versus oral ibuprofen + oral paracetamol, Outcome 1 Clearance.

Comparison 22 Oral propranolol versus oral ibuprofen + oral paracetamol, Outcome 2 Adverse events.
Figures and Tables -
Analysis 22.2

Comparison 22 Oral propranolol versus oral ibuprofen + oral paracetamol, Outcome 2 Adverse events.

Comparison 22 Oral propranolol versus oral ibuprofen + oral paracetamol, Outcome 3 Other measures of resolution: mean size of ulceration.
Figures and Tables -
Analysis 22.3

Comparison 22 Oral propranolol versus oral ibuprofen + oral paracetamol, Outcome 3 Other measures of resolution: mean size of ulceration.

Comparison 23 Oral propranolol + topical timolol maleate versus oral propranolol, Outcome 1 Adverse events in general.
Figures and Tables -
Analysis 23.1

Comparison 23 Oral propranolol + topical timolol maleate versus oral propranolol, Outcome 1 Adverse events in general.

Comparison 23 Oral propranolol + topical timolol maleate versus oral propranolol, Outcome 2 Other measures of resolution: colour fading/visual analogue scale score.
Figures and Tables -
Analysis 23.2

Comparison 23 Oral propranolol + topical timolol maleate versus oral propranolol, Outcome 2 Other measures of resolution: colour fading/visual analogue scale score.

Comparison 23 Oral propranolol + topical timolol maleate versus oral propranolol, Outcome 3 Other measures of resolution: size reduction/visual analogue scale score.
Figures and Tables -
Analysis 23.3

Comparison 23 Oral propranolol + topical timolol maleate versus oral propranolol, Outcome 3 Other measures of resolution: size reduction/visual analogue scale score.

Comparison 23 Oral propranolol + topical timolol maleate versus oral propranolol, Outcome 4 Other measures of resolution: size reduction > 50%.
Figures and Tables -
Analysis 23.4

Comparison 23 Oral propranolol + topical timolol maleate versus oral propranolol, Outcome 4 Other measures of resolution: size reduction > 50%.

Comparison 24 Oral propranolol + topical timolol maleate versus topical timolol maleate, Outcome 1 Adverse events.
Figures and Tables -
Analysis 24.1

Comparison 24 Oral propranolol + topical timolol maleate versus topical timolol maleate, Outcome 1 Adverse events.

Comparison 24 Oral propranolol + topical timolol maleate versus topical timolol maleate, Outcome 2 Other measures of resolution: size reduction > 50%.
Figures and Tables -
Analysis 24.2

Comparison 24 Oral propranolol + topical timolol maleate versus topical timolol maleate, Outcome 2 Other measures of resolution: size reduction > 50%.

Comparison 25 Oral prednisolone versus oral prednisolone + oral propranolol, Outcome 1 Adverse events: complications.
Figures and Tables -
Analysis 25.1

Comparison 25 Oral prednisolone versus oral prednisolone + oral propranolol, Outcome 1 Adverse events: complications.

Comparison 25 Oral prednisolone versus oral prednisolone + oral propranolol, Outcome 2 Other measures of resolution: colour fading.
Figures and Tables -
Analysis 25.2

Comparison 25 Oral prednisolone versus oral prednisolone + oral propranolol, Outcome 2 Other measures of resolution: colour fading.

Comparison 25 Oral prednisolone versus oral prednisolone + oral propranolol, Outcome 3 Other measures of resolution: mean size reduction.
Figures and Tables -
Analysis 25.3

Comparison 25 Oral prednisolone versus oral prednisolone + oral propranolol, Outcome 3 Other measures of resolution: mean size reduction.

Comparison 26 Intralesional methylene blue versus intralesional triamcinolone, Outcome 1 Clearance.
Figures and Tables -
Analysis 26.1

Comparison 26 Intralesional methylene blue versus intralesional triamcinolone, Outcome 1 Clearance.

Comparison 27 Oral prednisolone versus intravenous methylprednisolone, Outcome 1 Other measures of resolution: haemangioma size.
Figures and Tables -
Analysis 27.1

Comparison 27 Oral prednisolone versus intravenous methylprednisolone, Outcome 1 Other measures of resolution: haemangioma size.

Comparison 28 HIFU 3.5 W versus HIFU 4.5 W, Outcome 1 Clearance.
Figures and Tables -
Analysis 28.1

Comparison 28 HIFU 3.5 W versus HIFU 4.5 W, Outcome 1 Clearance.

Comparison 28 HIFU 3.5 W versus HIFU 4.5 W, Outcome 2 Adverse events: ulceration or scars.
Figures and Tables -
Analysis 28.2

Comparison 28 HIFU 3.5 W versus HIFU 4.5 W, Outcome 2 Adverse events: ulceration or scars.

Comparison 29 HIFU 3.5 W versus HIFU 4.0 W, Outcome 1 Clearance.
Figures and Tables -
Analysis 29.1

Comparison 29 HIFU 3.5 W versus HIFU 4.0 W, Outcome 1 Clearance.

Comparison 29 HIFU 3.5 W versus HIFU 4.0 W, Outcome 2 Adverse events: ulceration or scars.
Figures and Tables -
Analysis 29.2

Comparison 29 HIFU 3.5 W versus HIFU 4.0 W, Outcome 2 Adverse events: ulceration or scars.

Comparison 30 HIFU 4.0 W versus HIFU 4.5 W, Outcome 1 Clearance.
Figures and Tables -
Analysis 30.1

Comparison 30 HIFU 4.0 W versus HIFU 4.5 W, Outcome 1 Clearance.

Comparison 30 HIFU 4.0 W versus HIFU 4.5 W, Outcome 2 Adverse events: ulceration or scars.
Figures and Tables -
Analysis 30.2

Comparison 30 HIFU 4.0 W versus HIFU 4.5 W, Outcome 2 Adverse events: ulceration or scars.

Summary of findings for the main comparison. Oral propranolol compared to placebo for infantile haemangiomas of the skin

Oral propranolol compared to placebo for infantile haemangiomas (strawberry birthmarks) of the skin

Patient or population: infantile haemangiomas (strawberry birthmarks) of the skin
Setting: all settings (outpatient care)
Intervention: oral propranolol
Comparison: placebo

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with placebo

Risk with oral propranolol

Clearance, as assessed by a clinician at any follow‐up ‐ 3 mg/kg/day

24 weeks' follow‐up

36 per 1000

604 per 1000
(153 to 1000)

RR 16.61
(4.22 to 65.34)

156
(1 RCT)

⊕⊕⊝⊝
MODERATE1

A subjective measure of improvement, as assessed by the parent or child, at any follow‐up ‐ not reported

See comment

See comment

Not estimable

See comment

We did not identify any studies reporting this outcome.

Adverse events experienced at short or long term ‐ Serious adverse events

24 weeks' follow‐up

37 per 1000

38 per 1000
(12 to 124)

RR 1.05
(0.33 to 3.39)

509
(3 RCTs)

⊕⊝⊝⊝
LOW2

Other measures of resolution, as assessed by a clinician, at any follow‐up ‐ percentage change in mean haemangioma volume at 24 weeks

Mean: ‐14.1% (SD not reported)

Mean: ‐60% (SD not reported)

MD

45.9% lower

(80.2% lower to 11.6% lower)

40
(1 RCT)

⊕⊕⊕⊝
MODERATE3

Mean difference was reported by the study authors, but no SDs were reported for group means.

Proportion of parents who consider their child still has a problem, at any follow‐up ‐ not reported

See comment

See comment

Not estimable

See comment

We did not identify any studies reporting this outcome.

Proportion of children who consider they still have a problem, at any follow‐up ‐ not reported

See comment

See comment

Not estimable

See comment

We did not identify any studies reporting this outcome.

Aesthetic appearance as assessed by physician, child, or parent, at any follow‐up ‐ not reported

See comment

See comment

Not estimable

See comment

We did not identify any studies reporting this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group (the event rate in the single study or the mean event rate in the meta‐analysis) and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio; SD: standard deviation

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

1Downgraded by one level for imprecision (wide confidence interval around the estimate of the effect).
2Downgraded by two levels for imprecision (wide confidence interval around the estimate of the effect and low number of events).
3Downgraded by one level for risk of bias.

Figures and Tables -
Summary of findings for the main comparison. Oral propranolol compared to placebo for infantile haemangiomas of the skin
Summary of findings 2. Topical timolol compared to placebo for infantile haemangiomas of the skin

Topical timolol maleate compared to placebo for infantile haemangiomas (strawberry birthmarks) of the skin

Patient or population: infantile haemangiomas (strawberry birthmarks) of the skin
Setting: all settings (outpatient care)
Intervention: topical timolol maleate
Comparison: placebo

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with placebo

Risk with topical timolol maleate

Clearance, as assessed by a clinician at any follow‐up ‐ not reported

See comment

See comment

Not estimable

See comment

We did not identify any studies reporting this outcome.

A subjective measure of improvement, as assessed by the parent or child, at any follow‐up ‐ not reported

See comment

See comment

Not estimable

See comment

We did not identify any studies reporting this outcome.

Adverse events experienced at short or long term ‐

Serious cardiovascular adverse events ‐ bradycardia

24 weeks' follow‐up

See comment

See comment

Not estimable

41
(1 RCT)

⊕⊕⊝⊝
LOW1

No events of bradycardia reported in Chan 2013.

Other measures of resolution, as assessed by a clinician, at any follow‐up ‐ no redness

45 per 1000

369 per 1000
(50 to 1000)

RR 8.11
(1.09 to 60.09)

41
(1 RCT)

⊕⊕⊝⊝
LOW2

Proportion of parents who consider their child still has a problem, at any follow‐up ‐ not reported

See comment

See comment

Not estimable

See comment

We did not identify any studies reporting this outcome.

Proportion of children who consider they still have a problem, at any follow‐up ‐ not reported

See comment

See comment

Not estimable

See comment

We did not identify any studies reporting this outcome.

Aesthetic appearance as assessed by physician, child, or parent, at any follow‐up ‐ not reported

See comment

See comment

Not estimable

See comment

We did not identify any studies reporting this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group (the event rate in the single study) and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

1Downgraded by two levels for imprecision (low number of participants and events).
2Downgraded by two levels for imprecision (wide confidence interval around the estimate of the effect and low number of participants and events).

Figures and Tables -
Summary of findings 2. Topical timolol compared to placebo for infantile haemangiomas of the skin
Summary of findings 3. Oral propranolol compared to topical timolol for infantile haemangiomas of the skin

Oral propranolol compared to topical timolol maleate for infantile haemangiomas (strawberry birthmarks) of the skin

Patient or population: infantile haemangiomas (strawberry birthmarks) of the skin
Setting: all settings (outpatient care)
Intervention: oral propranolol
Comparison: topical timolol maleate

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with topical timolol maleate

Risk with oral propranolol

Clearance, as assessed by a clinician at any follow‐up ‐ not reported

See comment

See comment

Not estimable

See comment

We did not identify any studies reporting this outcome.

A subjective measure of improvement, as assessed by the parent or child, at any follow‐up ‐ not reported

See comment

See comment

Not estimable

See comment

We did not identify any studies reporting this outcome.

Adverse events experienced at short or long term ‐ general adverse events

24 weeks' follow‐up

See comment

See comment

RR 7.00
(0.40 to 123.35)

26
(1 RCT)

⊕⊝⊝⊝
VERY LOW1

There were 3 events in the oral propranolol group and no events in the topical timolol maleate group. Due to no events in the control group, absolute events could not be calculated.

Other measures of resolution, as assessed by a clinician, at any follow‐up ‐ size reduction ≥ 50%

24 weeks' follow up

615 per 1000

695 per 1000
(394 to 1000)

RR 1.13
(0.64 to 1.97)

26
(1 RCT)

⊕⊕⊝⊝
LOW2

Proportion of parents who consider their child still has a problem, at any follow‐up ‐ not reported

See comment

See comment

Not estimable

See comment

We did not identify any studies reporting this outcome.

Proportion of children who consider they still have a problem, at any follow‐up ‐ not reported

See comment

See comment

Not estimable

See comment

We did not identify any studies reporting this outcome.

Aesthetic appearance as assessed by physician, child, or parent, at any follow‐up ‐ not reported

See comment

See comment

Not estimable

See comment

We did not identify any studies reporting this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group (the event rate in the single study) and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

1Downgraded by three levels: one level due to unclear risk of selection and performance bias and two levels for imprecision (wide confidence interval around the estimate of the effect and low number of participants and events).
2Downgraded by two levels: one level due to unclear risk of selection and performance bias and one level for imprecision (small sample size).

Figures and Tables -
Summary of findings 3. Oral propranolol compared to topical timolol for infantile haemangiomas of the skin
Comparison 1. Pulsed dye laser versus wait‐and‐see

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance Show forest plot

1

121

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.62, 1.42]

2 Adverse events: skin atrophy Show forest plot

1

121

Risk Ratio (M‐H, Random, 95% CI)

3.46 [1.36, 8.77]

3 Adverse events: skin hypopigmentation Show forest plot

1

121

Risk Ratio (M‐H, Random, 95% CI)

3.05 [1.57, 5.93]

4 Adverse events: minimal crusting Show forest plot

1

22

Risk Ratio (M‐H, Random, 95% CI)

5.0 [0.27, 93.55]

5 Adverse events: pain Show forest plot

1

22

Risk Ratio (M‐H, Random, 95% CI)

5.0 [0.27, 93.55]

6 Other measures of resolution: no redness Show forest plot

1

121

Risk Ratio (M‐H, Random, 95% CI)

4.83 [1.75, 13.36]

7 Parents who consider that their child still has a problem Show forest plot

1

121

Risk Ratio (M‐H, Random, 95% CI)

1.24 [0.56, 2.78]

8 Aesthetic appearance: better cosmetic outcome Show forest plot

1

22

Risk Ratio (M‐H, Random, 95% CI)

1.75 [0.71, 4.31]

9 Requirement for surgical correction Show forest plot

1

121

Risk Ratio (M‐H, Random, 95% CI)

2.37 [0.64, 8.75]

Figures and Tables -
Comparison 1. Pulsed dye laser versus wait‐and‐see
Comparison 2. Oral propranolol versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance, as assessed by a clinician Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 At 1 mg/kg/day

1

157

Risk Ratio (M‐H, Random, 95% CI)

13.48 [3.41, 53.30]

1.2 At 3 mg/kg/day

1

156

Risk Ratio (M‐H, Random, 95% CI)

16.61 [4.22, 65.34]

2 Serious adverse events Show forest plot

3

509

Risk Ratio (M‐H, Random, 95% CI)

1.05 [0.33, 3.39]

3 Serious cardiovascular adverse events Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

3.1 Bradycardia

3

509

Risk Ratio (M‐H, Random, 95% CI)

0.70 [0.03, 14.32]

3.2 Hypotension

3

509

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.10, 6.71]

4 Other adverse events Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

4.1 Bronchospasm

1

456

Risk Ratio (M‐H, Random, 95% CI)

0.41 [0.04, 3.89]

4.2 Bronchitis

1

456

Risk Ratio (M‐H, Random, 95% CI)

5.62 [0.79, 40.07]

4.3 Bronchiolitis

1

456

Risk Ratio (M‐H, Random, 95% CI)

1.33 [0.42, 4.21]

4.4 Hypoglycaemia

1

456

Risk Ratio (M‐H, Random, 95% CI)

0.70 [0.03, 14.32]

4.5 Sleep disturbance

2

495

Risk Ratio (M‐H, Random, 95% CI)

1.54 [0.79, 3.00]

5 Other measures of resolution: change in volume Show forest plot

1

Mean Difference (Random, 95% CI)

‐45.9 [‐80.20, ‐11.60]

6 Other measures of resolution: no improvement in redness Show forest plot

1

40

Risk Ratio (M‐H, Random, 95% CI)

9.00 [0.52, 156.91]

Figures and Tables -
Comparison 2. Oral propranolol versus placebo
Comparison 3. Topical timolol maleate versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Other measures of resolution (6 months) Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 No redness

1

41

Risk Ratio (M‐H, Random, 95% CI)

8.11 [1.09, 60.09]

1.2 IH volume reduction of ≥ 5%

1

41

Risk Ratio (M‐H, Random, 95% CI)

5.21 [1.28, 21.21]

Figures and Tables -
Comparison 3. Topical timolol maleate versus placebo
Comparison 4. Topical bleomycin versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Other measures of resolution: reduction in size at day 7 Show forest plot

1

30

Risk Ratio (M‐H, Random, 95% CI)

21.0 [1.34, 328.86]

Figures and Tables -
Comparison 4. Topical bleomycin versus placebo
Comparison 5. X‐ray radiation versus sham radiation

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance Show forest plot

1

100

Risk Ratio (M‐H, Random, 95% CI)

1.08 [0.63, 1.87]

Figures and Tables -
Comparison 5. X‐ray radiation versus sham radiation
Comparison 6. Topical timolol maleate versus Nd:YAG laser

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Other measures of resolution (continuous) Show forest plot

1

60

Mean Difference (IV, Random, 95% CI)

‐0.91 [‐1.27, ‐0.55]

1.1 Haemoglobin level (redness)

1

60

Mean Difference (IV, Random, 95% CI)

‐0.91 [‐1.27, ‐0.55]

2 Other measures of resolution (dichotomous) Show forest plot

1

60

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.90, 10.01]

2.1 Excellent improvement

1

60

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.90, 10.01]

Figures and Tables -
Comparison 6. Topical timolol maleate versus Nd:YAG laser
Comparison 7. Nd:YAG laser versus oral propranolol

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance Show forest plot

1

65

Risk Ratio (M‐H, Random, 95% CI)

2.57 [0.28, 23.44]

2 Adverse events: hyperpigmentation Show forest plot

1

65

Risk Ratio (M‐H, Random, 95% CI)

2.57 [0.28, 23.44]

3 Adverse event: pigmentation and thinning Show forest plot

1

40

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.11, 1.05]

4 Adverse events: superficial scar Show forest plot

2

105

Risk Ratio (M‐H, Random, 95% CI)

1.52 [0.24, 9.58]

5 Other measures of resolution: excellent response Show forest plot

1

40

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.08, 1.46]

Figures and Tables -
Comparison 7. Nd:YAG laser versus oral propranolol
Comparison 8. Pulsed dye laser + topical propranolol versus pulsed dye laser

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance, as assessed by a clinician Show forest plot

1

19

Risk Ratio (M‐H, Random, 95% CI)

2.25 [0.57, 8.86]

Figures and Tables -
Comparison 8. Pulsed dye laser + topical propranolol versus pulsed dye laser
Comparison 9. Pulsed dye laser + topical timolol maleate versus pulsed dye laser

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance Show forest plot

1

32

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.07, 14.64]

2 Other measures of resolution: mean size reduction Show forest plot

1

32

Mean Difference (IV, Random, 95% CI)

5.62 [1.21, 10.03]

Figures and Tables -
Comparison 9. Pulsed dye laser + topical timolol maleate versus pulsed dye laser
Comparison 10. Nd:YAG laser + oral propranolol versus Nd:YAG laser

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance Show forest plot

1

67

Risk Ratio (M‐H, Random, 95% CI)

3.28 [0.97, 11.06]

2 Adverse events: hyperpigmentation Show forest plot

1

67

Risk Ratio (M‐H, Random, 95% CI)

1.46 [0.35, 6.02]

3 Adverse events: pigmentation and thinning Show forest plot

1

40

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.12, 3.57]

4 Adverse events: superficial scar Show forest plot

2

107

Risk Ratio (M‐H, Random, 95% CI)

0.37 [0.09, 1.48]

5 Other measures of resolution: excellent response Show forest plot

1

40

Risk Ratio (M‐H, Random, 95% CI)

8.5 [2.25, 32.06]

Figures and Tables -
Comparison 10. Nd:YAG laser + oral propranolol versus Nd:YAG laser
Comparison 11. Nd:YAG laser + oral propranolol versus oral propranolol

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance Show forest plot

1

62

Risk Ratio (M‐H, Random, 95% CI)

8.44 [1.14, 62.66]

2 Adverse events: hyperpigmentation Show forest plot

1

62

Risk Ratio (M‐H, Random, 95% CI)

3.75 [0.44, 31.68]

3 Adverse events: pigmentation and thinning Show forest plot

1

40

Risk Ratio (M‐H, Random, 95% CI)

0.22 [0.05, 0.90]

4 Adverse events: superficial scar Show forest plot

2

102

Risk Ratio (M‐H, Random, 95% CI)

0.60 [0.05, 7.63]

5 Other measures of resolution: excellent response Show forest plot

1

40

Risk Ratio (M‐H, Random, 95% CI)

2.83 [1.42, 5.67]

Figures and Tables -
Comparison 11. Nd:YAG laser + oral propranolol versus oral propranolol
Comparison 12. ⁹⁰SR‐⁹⁰Y radiation + topical timolol maleate versus ⁹⁰SR‐⁹⁰Y radiation

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance Show forest plot

1

72

Risk Ratio (M‐H, Random, 95% CI)

1.42 [1.07, 1.87]

2 Adverse events Show forest plot

1

72

Risk Ratio (M‐H, Random, 95% CI)

1.14 [0.56, 2.29]

Figures and Tables -
Comparison 12. ⁹⁰SR‐⁹⁰Y radiation + topical timolol maleate versus ⁹⁰SR‐⁹⁰Y radiation
Comparison 13. Sequential dual‐wavelength laser + oral propranolol versus concurrent dual‐wavelength laser + oral propranolol

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Other outcomes of resolution: mean efficacy rating Show forest plot

1

61

Mean Difference (IV, Random, 95% CI)

‐0.77 [‐1.16, ‐0.38]

Figures and Tables -
Comparison 13. Sequential dual‐wavelength laser + oral propranolol versus concurrent dual‐wavelength laser + oral propranolol
Comparison 14. Oral propranolol versus topical propranolol

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance Show forest plot

1

30

Risk Ratio (M‐H, Random, 95% CI)

3.0 [1.01, 8.95]

2 Adverse events: syncopal attack Show forest plot

1

30

Risk Ratio (M‐H, Random, 95% CI)

7.0 [0.39, 124.83]

Figures and Tables -
Comparison 14. Oral propranolol versus topical propranolol
Comparison 15. Oral propranolol versus intralesional propranolol

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance Show forest plot

1

30

Risk Ratio (M‐H, Random, 95% CI)

4.5 [1.16, 17.44]

2 Adverse events: syncopal attack Show forest plot

1

30

Risk Ratio (M‐H, Random, 95% CI)

7.0 [0.39, 124.83]

Figures and Tables -
Comparison 15. Oral propranolol versus intralesional propranolol
Comparison 16. Topical propranolol versus intralesional propranolol

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance Show forest plot

1

30

Risk Ratio (M‐H, Random, 95% CI)

1.5 [0.29, 7.73]

Figures and Tables -
Comparison 16. Topical propranolol versus intralesional propranolol
Comparison 17. Oral atenolol versus oral propranolol

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance Show forest plot

1

23

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.55, 2.27]

Figures and Tables -
Comparison 17. Oral atenolol versus oral propranolol
Comparison 18. Oral propranolol versus oral prednisolone

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Severe adverse events Show forest plot

1

19

Risk Ratio (M‐H, Random, 95% CI)

0.15 [0.02, 1.02]

2 Adverse events: complications in general Show forest plot

1

20

Risk Ratio (M‐H, Random, 95% CI)

0.22 [0.06, 0.78]

3 Other measures of resolution: colour fading Show forest plot

1

20

Mean Difference (IV, Random, 95% CI)

‐1.0 [‐3.08, 1.08]

4 Other measures of resolution: mean size reduction Show forest plot

1

20

Mean Difference (IV, Random, 95% CI)

23.20 [‐3.36, 49.76]

5 Other measures of resolution: proportional change in the total surface area Show forest plot

1

19

Mean Difference (IV, Random, 95% CI)

0.23 [‐0.08, 0.54]

Figures and Tables -
Comparison 18. Oral propranolol versus oral prednisolone
Comparison 19. Oral propranolol versus oral captopril

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance Show forest plot

1

30

Risk Ratio (M‐H, Random, 95% CI)

15.0 [0.93, 241.20]

2 Adverse events: cardiac side effects Show forest plot

1

30

Risk Ratio (M‐H, Random, 95% CI)

0.11 [0.01, 1.90]

Figures and Tables -
Comparison 19. Oral propranolol versus oral captopril
Comparison 20. Oral propranolol versus topical timolol maleate

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Adverse events Show forest plot

1

26

Risk Ratio (M‐H, Random, 95% CI)

7.0 [0.40, 123.35]

2 Other measures of resolution: size reduction > 50% Show forest plot

1

26

Risk Ratio (M‐H, Random, 95% CI)

1.13 [0.64, 1.97]

Figures and Tables -
Comparison 20. Oral propranolol versus topical timolol maleate
Comparison 21. Oral propranolol versus oral propranolol + oral prednisolone

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Adverse events in general Show forest plot

2

60

Risk Ratio (M‐H, Random, 95% CI)

0.30 [0.10, 0.91]

2 Other measures of resolution: mean size reduction Show forest plot

1

20

Mean Difference (IV, Random, 95% CI)

7.20 [‐1.87, 16.27]

3 Other measures of resolution: decrease in redness Show forest plot

1

40

Risk Ratio (M‐H, Random, 95% CI)

0.77 [0.45, 1.32]

Figures and Tables -
Comparison 21. Oral propranolol versus oral propranolol + oral prednisolone
Comparison 22. Oral propranolol versus oral ibuprofen + oral paracetamol

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance Show forest plot

1

64

Risk Ratio (M‐H, Random, 95% CI)

2.67 [0.78, 9.15]

2 Adverse events Show forest plot

1

64

Risk Ratio (M‐H, Random, 95% CI)

7.0 [0.38, 130.26]

3 Other measures of resolution: mean size of ulceration Show forest plot

1

64

Mean Difference (IV, Random, 95% CI)

0.31 [0.01, 0.61]

Figures and Tables -
Comparison 22. Oral propranolol versus oral ibuprofen + oral paracetamol
Comparison 23. Oral propranolol + topical timolol maleate versus oral propranolol

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Adverse events in general Show forest plot

1

26

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.04, 2.80]

2 Other measures of resolution: colour fading/visual analogue scale score Show forest plot

1

31

Mean Difference (IV, Random, 95% CI)

1.18 [0.09, 2.27]

3 Other measures of resolution: size reduction/visual analogue scale score Show forest plot

1

31

Mean Difference (IV, Random, 95% CI)

0.41 [‐0.84, 1.66]

4 Other measures of resolution: size reduction > 50% Show forest plot

1

26

Risk Ratio (M‐H, Random, 95% CI)

1.22 [0.79, 1.88]

Figures and Tables -
Comparison 23. Oral propranolol + topical timolol maleate versus oral propranolol
Comparison 24. Oral propranolol + topical timolol maleate versus topical timolol maleate

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Adverse events Show forest plot

1

26

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.13, 67.51]

2 Other measures of resolution: size reduction > 50% Show forest plot

1

26

Risk Ratio (M‐H, Random, 95% CI)

1.38 [0.84, 2.24]

Figures and Tables -
Comparison 24. Oral propranolol + topical timolol maleate versus topical timolol maleate
Comparison 25. Oral prednisolone versus oral prednisolone + oral propranolol

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Adverse events: complications Show forest plot

1

20

Risk Ratio (M‐H, Random, 95% CI)

1.29 [0.82, 2.03]

2 Other measures of resolution: colour fading Show forest plot

1

20

Mean Difference (IV, Random, 95% CI)

1.0 [‐1.02, 3.02]

3 Other measures of resolution: mean size reduction Show forest plot

1

20

Mean Difference (IV, Random, 95% CI)

‐16.0 [‐42.58, 10.58]

Figures and Tables -
Comparison 25. Oral prednisolone versus oral prednisolone + oral propranolol
Comparison 26. Intralesional methylene blue versus intralesional triamcinolone

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance Show forest plot

1

268

Risk Ratio (M‐H, Random, 95% CI)

2.36 [1.84, 3.02]

Figures and Tables -
Comparison 26. Intralesional methylene blue versus intralesional triamcinolone
Comparison 27. Oral prednisolone versus intravenous methylprednisolone

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Other measures of resolution: haemangioma size Show forest plot

1

20

Mean Difference (IV, Random, 95% CI)

51.5 [21.49, 81.51]

Figures and Tables -
Comparison 27. Oral prednisolone versus intravenous methylprednisolone
Comparison 28. HIFU 3.5 W versus HIFU 4.5 W

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance Show forest plot

1

40

Risk Ratio (M‐H, Random, 95% CI)

0.88 [0.39, 1.95]

2 Adverse events: ulceration or scars Show forest plot

1

40

Risk Ratio (M‐H, Random, 95% CI)

0.07 [0.00, 1.09]

Figures and Tables -
Comparison 28. HIFU 3.5 W versus HIFU 4.5 W
Comparison 29. HIFU 3.5 W versus HIFU 4.0 W

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance Show forest plot

1

40

Risk Ratio (M‐H, Random, 95% CI)

0.78 [0.36, 1.68]

2 Adverse events: ulceration or scars Show forest plot

1

40

Risk Ratio (M‐H, Random, 95% CI)

0.11 [0.01, 1.94]

Figures and Tables -
Comparison 29. HIFU 3.5 W versus HIFU 4.0 W
Comparison 30. HIFU 4.0 W versus HIFU 4.5 W

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clearance Show forest plot

1

40

Risk Ratio (M‐H, Random, 95% CI)

1.13 [0.55, 2.32]

2 Adverse events: ulceration or scars Show forest plot

1

40

Risk Ratio (M‐H, Random, 95% CI)

0.57 [0.20, 1.65]

Figures and Tables -
Comparison 30. HIFU 4.0 W versus HIFU 4.5 W