Van der Aa 2010.

Methods	Twelve‐week multi‐centre parallel‐group double‐blind placebo‐controlled randomised trial
Participants	Ninety infants 0 to 7 months of age, exclusively formula fed, with a diagnosis of atopic dermatitis based on Hanifin and Rajka diagnostic criteria and SCORAD > 15 were recruited in the study. Randomisation was done at a 1:1 ratio: 46 participants were randomised in the intervention arm, and 44 in the control arm Infants who had received systemic corticosteroids, antibiotics, antimycotics, calcineurin inhibitors, or probiotics during 4 weeks or antihistamines during 2 weeks before enrolment were excluded from the study. Also excluded were infants needing systemic treatments other than antibiotics during the study and infants with major medical problems or GI or skin conditions other than atopic dermatitis Setting: participants recruited at 7 paediatric and dermatology secondary care centres in the Netherlands Eight participants were lost to follow‐up. Five participants (4 in the symbiotic group and 1 in the placebo group) were excluded from analysis because no SCORAD assessment was undertaken after baseline assessment
Interventions	Synbiotic: extensively hydrolysed whey‐based formula with Bifidobacterium breve M‐16V with 90% scGOS and 10% lcFOS given on demand at a dose of 1.3 × 10⁹ CFUs/100 mL of probiotic and 0.8 gr/100 mL of prebiotic for 12 weeks Placebo: formula given only on demand for 12 weeks
Outcomes	• Changes in total SCORAD from baseline to 4, 8, and 12 (end of treatment) weeks* • Total SCORAD in 1 year after the intervention • Frequency and mean class of topical steroids used at baseline and at end of treatment* *Denotes outcomes prespecified for this review
Notes	Two participants experienced severe adverse events: RSV bronchiolitis and severe cow's milk allergy. These were not related to the intervention Sponsored by a probiotic/formula company
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Participants were randomised, using computer‐generated 4‐blocked design lists, drawn up by a statistician with stratification according to recruiting hospital and current use of topical steroids..." Comment: judged as adequate for low risk of bias
Allocation concealment (selection bias)	Low risk	Quote: "Formulas were prepared and coded by Danone Research and dispensed by the pharmacy of the Academic Medical Centre", "both formulas were identical with respect to smell, taste, texture, colour and packaging" Comment: third party involved; judged as adequate for low risk of bias
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quotes: "both formulas were identical with respect to smell, taste, texture, colour and packaging. The investigator, participants' own physicians and parents were all blind to the treatment groups" Comment: judged as adequate for low risk of bias
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The investigator, participants' own physicians and parents were all blind to the treatment groups. Participants were clinically assessed by one investigator (L.B.A.), at weeks 0, 4, 8 and 12" Comment: judged as adequate for low risk of bias
Incomplete outcome data (attrition bias) All outcomes	Low risk	6/46 (13%) participants from the probiotic group and 2/44 (4.5%) from the placebo group discontinued treatment but were not excluded from analysis. Five participants (5.5%) were excluded post randomisation because of unavailable assessment data after baseline. Four were from the probiotic group, and one from the placebo group. Losses to follow‐up included in analysis but not certain how missing data were handled Comment: overall low rates of missing data; judged to have low risk of attrition bias
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Unclear risk	Sponsored by a probiotic/formula company. The role of the sponsor in data analysis is unclear; therefore the study was judged to be at unclear risk of bias