Timing of complementary feeding for early childhood allergy prevention: An overview of systematic reviews

Objective: To summarise and critically appraise systematic review (SR) evidence on the effects of timing of complementary feeding (CF) on the occurrence of allergic sensitisation and disease. Design: Overview of SRs. AMSTAR-2 and ROBIS were used to assess methodological quality and risk of bias (RoB) of SRs. RoB Tool 2.0 was used to assess RoB of primary randomised controlled trials (RCTs) (or extracted). The Certainty of Evidence (CoE) was assessed using GRADE. Findings were synthesised narratively. Data sources: MEDLINE (via PubMed and Ovid), the Cochrane Library and Web of Science Core Collection. Eligibility criteria: SRs investigating the effects of timing of CF on risk of developing food allergy (FA), allergic sensitisation, asthma, allergic rhinitis, atopic eczema, and adverse events in infants or young children (0-3 years), based on RCT evidence. Results: Eleven SRs were included, with predominantly low methodological quality and high RoB. Primary study overlap was very high for specific FA and slight to moderate for FA in general and other primary outcomes. Introducing specific foods (peanut, cooked egg) early probably reduces the risk of specific FA based on evidence across most SRs. The evidence for other allergic outcomes was mostly very uncertain and based on single primary studies. SRs varied regarding the timing of CF, the nature of complementary foods and the population risk, which limited comparability between SRs. Conclusions: The overlap of primary studies within SRs was high to very high for many outcomes, overemphasising single trials. Future research should focus on producing high quality trials and SRs that allow drawing more trustworthy conclusions. For developing guidelines to support decision-making on the timing of CF as a preventive strategy, the early introduction of specific foods (i.e., egg and peanut) seems promising and safe whereas more extensive research is required regarding other allergic outcomes and potential adverse events. Registration: PROSPERO (CRD42021240160); Open Science Forum (https://doi.org/10.17605/OSF.IO/HJKUN)