• Robert J Boyle, Despo Ierodiakonou, Tasnia Khan, Jennifer Chivinge, Zoe Robinson, Natalie Geoghegan, Katharine Jarrold, Thalia Afxentiou, Tim Reeves, Sergio Cunha, Marialena Trivella, Vanessa Garcia-Larsen, and Jo Leonardi-Bee.
• Section of Paediatrics, Imperial College London, London W2 1PG, UK r.boyle@nhs.net.
• BMJ. 2016 Mar 8; 352: i974.

ObjectiveTo determine whether feeding infants with hydrolysed formula reduces their risk of allergic or autoimmune disease.DesignSystematic review and meta-analysis, as part of a series of systematic reviews commissioned by the UK Food Standards Agency to inform guidelines on infant feeding. Two authors selected studies by consensus, independently extracted data, and assessed the quality of included studies using the Cochrane risk of bias tool.Data SourcesMedline, Embase, Web of Science, CENTRAL, and LILACS searched between January 1946 and April 2015.Eligibility Criteria For Selecting StudiesProspective intervention trials of hydrolysed cows' milk formula compared with another hydrolysed formula, human breast milk, or a standard cows' milk formula, which reported on allergic or autoimmune disease or allergic sensitisation.Results37 eligible intervention trials of hydrolysed formula were identified, including over 19,000 participants. There was evidence of conflict of interest and high or unclear risk of bias in most studies of allergic outcomes and evidence of publication bias for studies of eczema and wheeze. Overall there was no consistent evidence that partially or extensively hydrolysed formulas reduce risk of allergic or autoimmune outcomes in infants at high pre-existing risk of these outcomes. Odds ratios for eczema at age 0-4, compared with standard cows' milk formula, were 0.84 (95% confidence interval 0.67 to 1.07; I(2)=30%) for partially hydrolysed formula; 0.55 (0.28 to 1.09; I(2)=74%) for extensively hydrolysed casein based formula; and 1.12 (0.88 to 1.42; I(2)=0%) for extensively hydrolysed whey based formula. There was no evidence to support the health claim approved by the US Food and Drug Administration that a partially hydrolysed formula could reduce the risk of eczema nor the conclusion of the Cochrane review that hydrolysed formula could allergy to cows' milk.ConclusionThese findings do not support current guidelines that recommend the use of hydrolysed formula to prevent allergic disease in high risk infants.Review RegistrationPROSPERO CRD42013004252.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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