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Background  Despite evidence for the protective effects of early regular exposure to peanut and egg proteins against allergies, the optimal timing of cow's milk (CM) protein exposure is unknown.    Objective  We aimed to determine when during the first year of life CM‐based formula consumption becomes associated with lower CM allergy (CMA) risk.    Methods  We used the data set of the Japan Environment and Children's Study (JECS), a nationwide birth cohort involving over 100 000 mother‐child pairs. CMA was defined as an allergic reaction to a CM product in an individual not consuming CM products at the time of evaluation, combined with physician‐diagnosed food allergy. For each exposure, we identified when formula milk was commenced, and its consumption status during 0‐3, 3‐6 and 6‐12 months old.    Results  The prevalence of CMA was 0.23% and 1.03% at 6 and 12 months old, respectively. Multivariable regression analyses revealed that introducing regular consumption of formula within the first 3 months of age was associated with lower risk of CMA at 12 months. Regular consumption at 3‐6 months was strongly associated with a reduction in 12‐month CMA (adjusted relative risks [95% confidence intervals]: 0.22 [0.12‐0.35]), whereas no association was observed at 0‐3 months (1.07 [0.90‐1.27]).    Conclusion and Clinical Relevance  Regular exposure to formula milk at age 3 months or older is associated with lower CMA at 12 months old, suggesting that the effect of very early CM exposure on CMA may disappear if the exposure is brief. At present, however, the results of this observational study should not be used for formula recommendation and randomized controlled trials are required to confirm this association.

Possible association between early formula and reduced risk of cow’s milk allergy: The Japan Environment and Children’s Study