Introduction of allergenic food to infants and allergic and autoimmune conditions: a systematic review and meta-analysis

Tuballa A. December 2023. Introduction of allergenic food to infants and allergic and autoimmune conditions: a systematic review and meta-analysis. BMJ. doi: 10.1136/bmjebm-2023-112445

Objectives: To evaluate the effects of early introduction to allergenic foods compared with late introduction and its impact on food allergy, food sensitisation and autoimmune disease risk.

Design and setting: The systematic review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Four electronic databases (MEDLINE, CENTRAL, EMBASE and CINAHL) were searched from inception till 24 October 2022 using keywords and MeSH without limitations on publication's language or date. A forward and backwards citation analysis was also conducted. Risk of bias was assessed by three authors independently, in pairs using the Cochrane Risk of Bias Tool 2. Findings were narratively and quantitatively synthesised. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

Participants: Randomised controlled trials (RCTs) on allergenic food introduction prior to 12 months of age that evaluated its effect on the development of allergic and autoimmune conditions.

Intervention: Early introduction to allergenic foods to infants diet.

Main outcome measures: (1) Food allergy and sensitisation with main measures including oral food challenge, specific-IgE, skin prick testing, physician assessment and parental reporting. (2) Allergic and autoimmune conditions such as asthma and eczema.
Results: Of the 9060 identified records, we included 12 RCTs. We found high to moderate certainty evidence suggested that early introduction of allergen-containing foods reduces the risk of multiple food allergies (4 RCTs, 3854 participants, RR 0.49, 95% CI 0.33 to 0.74), egg (8 RCTs, 5193 participants, RR 0.58, 95% CI 0.44 to 0.78), peanut (3 RCTs, 4183 participants, RR 0.31, 95% CI 0.17 to 0.54) and atopic dermatitis or eczema (4 RCTs, 3579 participants, RR 0.88, 95% CI 0.78 to 1.00). Effects on other food allergies including milk, wheat, fish; autoimmune conditions, and food sensitisation are very uncertain and informed by low and very-low certainty evidence. No important subgroup differences were observed related to baseline risk of allergy and age at introduction. Sensitivity analyses limited to low risk of bias RCTs showed similar results.

Conclusions: This systematic review and meta-analysis shows that early introduction of allergen-containing food from 4 to 12 months of age, was associated with lower risk of multiple food allergy and eczema. Further research on other allergenic foods, and their long-term impact on food allergy and autoimmune risk is essential for enhancing our understanding on development of these conditions and guiding future clinical recommendations.