Early Introduction of Trace Amounts of Multiple Foods to Infants: A Randomized Double-Blind Study

Background: There is controversy regarding the efficacy and side effects of proactive administration of allergenic foods in early infancy to prevent food allergies. This is the first trial involving the gradual introduction of trace amounts of multiple foods to infants. Methods: Infants under 4 months old with atopic dermatitis from 14 primary care pediatric clinics in Japan were enrolled in this randomized, double-blind, placebo-controlled trial. The infants were administered either mixed allergenic food powder (MP) containing eggs, milk, wheat, soybeans, buckwheat, and peanuts, or placebo powder (PP). The amount of powder was increased in a stepwise manner on weeks 2 and 4 and continued until week 12. Weaning food was started subsequently according to the Japanese guidelines for nursing/bottle feeding, and for baby food. The occurrence of food allergy episodes after powder intervention was assessed at 18 months old by the physician responsible for each participant. Findings: A total of 163 participants were randomly allocated to either the MP group (n = 83, 50.9%) or the PP group (n = 80, 49.1%). There was a significant difference in the incidence of food allergy episodes by 18 months between the MP and PP groups (7/83 vs. 19/80, respectively; risk ratio 0.301 [95% CI 0.116 – 0.784]; P = 0.008). No serious adverse events attributable to MP were observed. Interpretation: Gradually increasing the intake of trace amounts of multiple foods in early infancy can safely reduce the incidence of food allergies. Clinical Trial Registration Details: UMIN000027837. The protocol for this study and the subsequent changes are available on the UMIN-CTR Trial website. Funding Information: This study was self-funded and did not receive any other support. Declaration of Interests: The authors declare that no conflicts of interest exist. Ethics Approval Statement: Written informed consent was obtained from the parents of the participants at the time of enrollment. The study was approved by the institutional review board of Umezu Clinic.