title: Timing of Allergenic Food Introduction to the Infant Diet and Risk of Allergic or Autoimmune Disease: A Systematic Review and Meta-analysis.
abstract: OBJECTIVE
  Timing of introduction of allergenic foods to the infant diet may influence the risk of allergic or autoimmune disease, but the evidence for this has not been comprehensively synthesized.
  
  
  OBJECTIVE
  To systematically review and meta-analyze evidence that timing of allergenic food introduction during infancy influences risk of allergic or autoimmune disease.
  
  
  METHODS
  MEDLINE, EMBASE, Web of Science, CENTRAL, and LILACS databases were searched between January 1946 and March 2016.
  
  
  METHODS
  Intervention trials and observational studies that evaluated timing of allergenic food introduction during the first year of life and reported allergic or autoimmune disease or allergic sensitization were included.
  
  
  METHODS
  Data were extracted in duplicate and synthesized for meta-analysis using generic inverse variance or Mantel-Haenszel methods with a random-effects model. GRADE was used to assess the certainty of evidence.
  
  
  METHODS
  Wheeze, eczema, allergic rhinitis, food allergy, allergic sensitization, type 1 diabetes mellitus, celiac disease, inflammatory bowel disease, autoimmune thyroid disease, and juvenile rheumatoid arthritis.
  
  
  RESULTS
  Of 16 289 original titles screened, data were extracted from 204 titles reporting 146 studies. There was moderate-certainty evidence from 5 trials (1915 participants) that early egg introduction at 4 to 6 months was associated with reduced egg allergy (risk ratio [RR], 0.56; 95% CI, 0.36-0.87; I2 = 36%; P = .009). Absolute risk reduction for a population with 5.4% incidence of egg allergy was 24 cases (95% CI, 7-35 cases) per 1000 population. There was moderate-certainty evidence from 2 trials (1550 participants) that early peanut introduction at 4 to 11 months was associated with reduced peanut allergy (RR, 0.29; 95% CI, 0.11-0.74; I2 = 66%; P = .009). Absolute risk reduction for a population with 2.5% incidence of peanut allergy was 18 cases (95% CI, 6-22 cases) per 1000 population. Certainty of evidence was downgraded because of imprecision of effect estimates and indirectness of the populations and interventions studied. Timing of egg or peanut introduction was not associated with risk of allergy to other foods. There was low- to very low-certainty evidence that early fish introduction was associated with reduced allergic sensitization and rhinitis. There was high-certainty evidence that timing of gluten introduction was not associated with celiac disease risk, and timing of allergenic food introduction was not associated with other outcomes.
  
  
  CONCLUSIONS
  In this systematic review, early egg or peanut introduction to the infant diet was associated with lower risk of developing egg or peanut allergy. These findings must be considered in the context of limitations in the primary studies.
authors.affiliation: Section of Paediatrics, Imperial College London, London, England2Respiratory Epidemiology, Imperial College London, London, England.
authors.forename: Despo
authors.initials: D
authors.lastname: Ierodiakonou
authors.affiliation: Respiratory Epidemiology, Imperial College London, London, England.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Garcia-Larsen
authors.affiliation: Section of Paediatrics, Imperial College London, London, England.
authors.forename: Andrew
authors.initials: A
authors.lastname: Logan
authors.affiliation: Section of Paediatrics, Imperial College London, London, England.
authors.forename: Annabel
authors.initials: A
authors.lastname: Groome
authors.affiliation: Respiratory Epidemiology, Imperial College London, London, England.
authors.forename: Sergio
authors.initials: S
authors.lastname: Cunha
authors.affiliation: Section of Paediatrics, Imperial College London, London, England.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chivinge
authors.affiliation: Section of Paediatrics, Imperial College London, London, England.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Robinson
authors.affiliation: Section of Paediatrics, Imperial College London, London, England.
authors.forename: Natalie
authors.initials: N
authors.lastname: Geoghegan
authors.affiliation: Section of Paediatrics, Imperial College London, London, England.
authors.forename: Katharine
authors.initials: K
authors.lastname: Jarrold
authors.affiliation: Respiratory Epidemiology, Imperial College London, London, England.
authors.forename: Tim
authors.initials: T
authors.lastname: Reeves
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland.
authors.forename: Nara
authors.initials: N
authors.lastname: Tagiyeva-Milne
authors.affiliation: University Division of Population Medicine, Cardiff University, Cardiff, Wales.
authors.forename: Ulugbek
authors.initials: U
authors.lastname: Nurmatov
authors.affiliation: Centre for Statistics in Medicine, University of Oxford, Oxford, England.
authors.forename: Marialena
authors.initials: M
authors.lastname: Trivella
authors.affiliation: Division of Epidemiology and Public Health, University of Nottingham, Nottingham, England.
authors.forename: Jo
authors.initials: J
authors.lastname: Leonardi-Bee
authors.affiliation: Section of Paediatrics, Imperial College London, London, England.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Boyle