for the main comparison.

Comparison: probiotics vs no probiotics for treating eczema
Patient or population: male and female patients 0 to 55 years of age with physician‐diagnosed eczema Settings: primary or secondary care. Europe: 22 studies with 1390 participants. Asia: 8 studies with 500 participants. Australasia: 2 studies with 116 participants Intervention: probiotics ± prebiotics Comparison: no probiotics
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	No probiotics	Probiotics
Primary outcome 1: participant‐ or parent‐rated symptoms of eczema (SCORAD part C) at the end of active treatment Visual analogue scale for itch and sleep disturbance ranging from 0 to 10 for each symptom and combined ranging from 0 to 20. The higher the score, the more severe the symptoms Duration of follow‐up from baseline until end of active treatment from 6 weeks to 3 months	Mean SCORAD part C score ranged across control groups from 2 to 7.9	Mean SCORAD part C score in the intervention groups was 0.44 points lower (1.22 lower to 0.33 higher)	‐	754 (13)	⊕⊕⊕⊝ moderatea	Two cross‐over studies included. Significant heterogeneity between studies Post hoc trial sequential analysis showed no effects of probiotics over control and suggests that further studies of currently available probiotic strains for this outcome may be futile
Primary outcome 1: participant‐ or parent‐rated global change in eczema symptoms at the end of active treatment (binary outcome) Change in risk for worsened/unchanged eczema Duration of follow‐up from baseline until end of active treatment from 6 weeks to 3 months	Low‐risk population		OR 0.40 (0.14 to 1.15)	135 (3)	⊕⊕⊝⊝ lowb	One cross‐over study included. Number of studies for this outcome was small. Moderate heterogeneity between studies
	300 per 1000	146 per 1000 (57 to 330)
	Medium‐risk population
	400 per 1000	210 per 1000 (85 to 434)
	High‐risk population
	500 per 1000	286 per 1000 (123 to 535)
Primary outcome 2: participant‐ or parent‐rated participant quality of life score at the end of active treatment Scales used: DLQI, IDQoL, Skindex‐29, CDLQI. On those scales, the higher the score, the more severely the quality of life is affected Duration of follow‐up from baseline until end of active treatment from 8 weeks to 3 months	Mean DLQI score ranged across control groups from 5.3 to 8.5	Mean participant quality of life score in the intervention groups was 0.03 standard deviations higher (0.36 lower to 0.42 higher)	‐	552 (6)	⊕⊕⊝⊝ lowc	Small number of studies for this outcome. Significant heterogeneity
Primary outcome 2: participant‐ or parent‐rated family quality of life score at the end of active treatment Scale used: DFI, FDLQI. On those scales, the higher the score, the more severely the quality of life is affected Duration of follow‐up from baseline until end of active treatment from 8 weeks to 3 months	Mean change in DFI score during treatment ranged across control groups from ‐2 points to ‐3 points	Mean family quality of life score in the intervention groups was 0.19 standard deviations lower (0.56 lower to 0.18 higher)	‐	358 (3)	⊕⊝⊝⊝ very lowd	Very small number of studies for this outcome. Significant heterogeneity
Secondary outcome 4: global eczema severity score (total SCORAD) at the end of active treatment (Investigator‐rated eczema severity) Scale used: total SCORAD ranging from 0 to 103. The higher the score, the more severe the disease Duration of follow‐up from baseline until end of active treatment from 8 weeks to 16 weeks	Mean total SCORAD ranged across control groups from 8.5 to 40.21 points	Mean total SCORAD score in the intervention groups was 3.91 points lower (5.86 to 1.96 points lower)	‐	1596 (24)	⊕⊕⊝⊝ lowe	Two cross‐over studies included. Extreme levels of heterogeneity for this outcome. Evidence of reporting bias
Secondary outcome 6: adverse events (gastrointestinal symptoms) during active treatment Duration of follow‐up from baseline until end of active treatment from 8 weeks to 3 months	Low‐risk population		RR 1.54 (0.90 to 2.63)	402 (7)	⊕⊕⊝⊝ lowf	Small number of studies reported adverse events. Small number of events were included in this analysis
	0 per 1000	0 per 1000 (0 to 0)
	Medium‐risk population
	100 per 1000	154 per 1000 (90 to 263)
	High‐risk population
	200 per 1000	308 per 1000 (180 to 526)
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CDLQI: Children's Dermatology Life Quality Index; CI: confidence interval; DFI: Dermatitis Family Impact; DLQI: Dermatology Life Quality Index; FDLQI: Family Dermatology Life Quality Index; IDQoL: Infant Dermatitis Quality of Life; OR: odds ratio; RR: risk ratio; SCORAD: Severity Scoring of Atopic Dermatitis.
GRADE Working Group grades of evidence. High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate.

^aDowngraded by one level due to inconsistency as there was significant heterogeneity among studies (I² = 57%).

^bDowngraded by two levels due to small number of studies for this outcome (imprecision) and because of moderate levels of heterogeneity among studies (I² = 48%).

^cDowngraded by two levels due to small number of studies for this outcome (imprecision) and because of significant levels of heterogeneity among studies (I² = 68%).

^dDowngraded by three levels due to inconsistency (one level) as there was significant heterogeneity among studies (I² = 57%) and because of very small number of studies (imprecision) for this outcome (two levels).

^eDowngraded by two levels because of extreme levels of heterogeneity among studies (I² = 79%) and because of evidence of reporting bias.

^fDowngraded by two levels because of small number of studies reporting adverse events and small number of events in the meta‐analysis for this outcome (imprecision).