title: Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis.
abstract: OBJECTIVE
  To determine whether feeding infants with hydrolysed formula reduces their risk of allergic or autoimmune disease.
  
  
  METHODS
  Systematic 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.
  
  
  METHODS
  Medline, Embase, Web of Science, CENTRAL, and LILACS searched between January 1946 and April 2015.
  
  
  METHODS
  Prospective 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.
  
  
  RESULTS
  37 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.
  
  
  CONCLUSIONS
  These findings do not support current guidelines that recommend the use of hydrolysed formula to prevent allergic disease in high risk infants.
  
  
  BACKGROUND
  PROSPERO CRD42013004252.
authors.affiliation: Section of Paediatrics, Imperial College London, London W2 1PG, UK r.boyle@nhs.net.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Boyle
authors.affiliation: Section of Paediatrics, Imperial College London, London W2 1PG, UK Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London SW3 6LR, UK.
authors.forename: Despo
authors.initials: D
authors.lastname: Ierodiakonou
authors.affiliation: Section of Paediatrics, Imperial College London, London W2 1PG, UK.
authors.forename: Tasnia
authors.initials: T
authors.lastname: Khan
authors.affiliation: Section of Paediatrics, Imperial College London, London W2 1PG, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chivinge
authors.affiliation: Section of Paediatrics, Imperial College London, London W2 1PG, UK.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Robinson
authors.affiliation: Section of Paediatrics, Imperial College London, London W2 1PG, UK.
authors.forename: Natalie
authors.initials: N
authors.lastname: Geoghegan
authors.affiliation: Section of Paediatrics, Imperial College London, London W2 1PG, UK.
authors.forename: Katharine
authors.initials: K
authors.lastname: Jarrold
authors.affiliation: Section of Paediatrics, Imperial College London, London W2 1PG, UK.
authors.forename: Thalia
authors.initials: T
authors.lastname: Afxentiou
authors.affiliation: Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London SW3 6LR, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Reeves
authors.affiliation: Imperial Consultants, London SW7 2PG, UK.
authors.forename: Sergio
authors.initials: S
authors.lastname: Cunha
authors.affiliation: Centre for Statistics in Medicine, University of Oxford, Oxford OX3 7LD, UK.
authors.forename: Marialena
authors.initials: M
authors.lastname: Trivella
authors.affiliation: Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London SW3 6LR, UK.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Garcia-Larsen
authors.affiliation: Division of Epidemiology and Public Health, University of Nottingham, Nottingham NG5 1PB, UK.
authors.forename: Jo
authors.initials: J
authors.lastname: Leonardi-Bee
mesh_terms: D001327:Autoimmune Diseases / Q000178:diet therapy / Q000209:etiology / Q000517:prevention & control*; D002364:Caseins / Q000008:administration & dosage* / Q000276:immunology*; D004044:Dietary Proteins / Q000008:administration & dosage / Q000276:immunology; D005512:Food Hypersensitivity / Q000178:diet therapy / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007108:Immune Tolerance; D007223:Infant; D041943:Infant Formula / Q000737:chemistry*; D007227:Infant Nutritional Physiological Phenomena; D007231:Infant, Newborn; D011446:Prospective Studies; D012306:Risk
chemical_list: D002364:Caseins; D004044:Dietary Proteins; C475729:casein hydrolysate