Gore 2011.
| Methods | Twelve‐week 3‐arm parallel‐group randomised double‐blind placebo‐controlled trial with follow‐up up to 36 months | |
| Participants | One hundred thirty‐seven infants between 3 and 6 months of age with physician‐diagnosed atopic dermatitis, in good general health, with normal growth, and consuming > 200 mL standard formula/d were recruited. Randomisation was done at a 1:2 ratio: 45 participants were randomised in the 2 intervention arms, and 45 in the control arm. SCORAD score at recruitment had to be ≥ 10 after standardised skin treatment for 2‐week run‐in period: 1% hydrocortisone ointment twice daily and emollients 2 to 4 times daily. Infants who were taking antibiotics or were on soya or extensively hydrolysed formula, those with congenital abnormalities or chronic disease, and those at less than 34 weeks' gestation were excluded from the trial Participants who were exclusively breastfed and those whose parents declined use of extensively hydrolysed formula were followed up as an open observational group Four participants were lost to follow‐up at 12 weeks Participants were recruited from primary care community clinics in the United Kingdom |
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| Interventions | First probiotic arm: Bifidobacterium lactis in powder sachets at a dose of 10¹º CFUs/d given with meals for 12 weeks Second probiotic arm: Lactobacillus paracasei in powder sachets at a dose of 10¹º CFUs/d given with meals for 12 weeks Placebo arm: maltodextrin in powder sachets given with meals for 12 weeks All arms followed a dairy elimination diet and used an extensively hydrolysed whey formula |
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| Outcomes | • Total SCORAD before 2‐week run‐in period, at baseline, at 4 and 12 weeks, and at 12, 18, and 36 months* • IDQoL before 2‐week run‐in period, at baseline, at 12 weeks, and at 12, 18, and 36 months* • Use of other eczema treatment at 12 weeks (end of intervention period)* • Number of infants receiving standard skin care: combination of topical steroids (TSs), emollients (≥ twice/d), and bath emollient* • Potency of TS* *Denotes outcomes prespecified for this review |
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| Notes | Funding and "no conflict of interest" declared Forty‐two out of 137 (30.7%) parents reported some difficulties, e.g. green loose stools, increased vomiting, feed refusal, or colic thought to be related to change in formula), and 24 of 137 (17.5%) stopped the formula |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Minimization method was applied to allocate subjects to study groups applying breast feeding, family history and initial SCORAD as stratification factors (TrialBalance randomisation programme; Nestec, Lausanne, Switzerland)" Comment: judged as adequate for low risk |
| Allocation concealment (selection bias) | Unclear risk | No information to confirm whether treatment allocation could be predicted |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | All interventions identical Blinding of clinicians confirmed by study author |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Confirmed by study author |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 2/45 (4.4%) participants inL paracasei group, 1/45 (2.2%) in B lactis group, and 1/47 (2.1%) in placebo group lost to follow‐up. 10/45 (22.2%) participants in L paracasei group, 9/45 in B lactis group, and 9/47 (19.1%) in placebo group stopped the study diet as per protocol but continued the intervention. Available case analysis used without exclusions, with imputation for missing data Comment: judged as unlikely to have influenced outcomes on eczema severity and quality of life, as similar and low rates of loss to follow‐up in all groups Also similar rates of stopping study formula in all groups |
| Selective reporting (reporting bias) | Low risk | All outcomes reported |
| Other bias | Low risk | No other bias found |