Timing of allergenic food introduction to the infant diet and risk of allergic or autoimmune disease: a systematic review and meta-analysis

Importance: Timing of allergenic food introduction to the infant diet may influence allergic or autoimmune disease risk, 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. Data Sources: MEDLINE, EMBASE, Web of Science, CENTRAL and LILACS, searched between January 1946 and March 2016. Study Selection: 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. Data Extraction and Synthesis: 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. Main Outcome(s) and Measure(s): 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 was associated with reduced egg allergy (RR 0.56 95%CI 0.36, 0.87I2=36%; P=0.009). Absolute risk reduction for a population with 5.4% incidence of egg allergy was 24 cases per 1000 population (95% CI 7, 35). There was moderate certainty evidence from 2 trials (1550 participants) that early peanut introduction was associated with reduced peanut allergy (RR 0.29 95%CI 0.11, 0.74 I2 56 =66%; P=0.009). Absolute risk reduction for a population with 2.5% incidence of peanut allergy was 18 cases per 1000 population (95% CI 6, 22). Certainty of evidence was downgraded due to 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 and Relevance: 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