Research in context
Evidence before this study
Since allergen avoidance in infancy has failed to prevent food allergy, early complementary introduction of allergenic foods was perceived as a more plausible primary prevention strategy. Allergic sensitisation is observed by age 4–6 months in some infants. Before the start of this study (December, 2014), data on the introduction of allergenic foods before 4 months of age for primary prevention of food allergy were scarce. In a systematic review from 2014, Da Silva and colleagues identified one cohort study by Venter and colleagues, who reported reduced food allergy or sensitisation to food when solids were introduced before age 4 months. Additionally, a Swedish randomised trial reported a reduction in allergy symptoms up to age 18 months in children fed cow's milk during the first few days of life, if both parents were atopic. We searched PubMed on Dec 15, 2020, without date or language restrictions, for clinical trials, randomised controlled trials, systematic reviews, and meta-analyses using the search term “primary prevention and ((atopic dermatitis or eczema) or (food allergy))”. Our search yielded 201 articles, of which 19 were considered relevant. Additionally, two relevant systematic review and meta-analyses from 2016 and 2020, and one randomised controlled trial published in January, 2021, were included in January, 2021. The Learning Early about Peanut Allergy trial done in 2015, showed that the consumption of peanuts in infants with atopic dermatitis or egg allergy, between age 4 months and 10 months, prevented peanut allergy. In the Enquiring About Tolerance trial, in which multiple allergenic foods were introduced in a general cohort of breastfed infants aged 3 months, no significant reduction in food allergy was identified between 1 and 36 months in the intention-to-treat analysis. However, among the 32% of infants who adhered to the food intervention, food allergy was significantly reduced, indicating that primary prevention through early complementary feeding from age 3 months might be possible. On the basis of 15 intervention trials, a 2016 systematic review and meta-analysis by Lerodiakonou and colleagues concluded with moderate-certainty evidence that the introduction of egg between 4 and 6 months of age reduced childhood allergy to egg, and the introduction of peanut between 4 and 11 months of age reduced childhood allergy to peanut. Two studies reported that early exposure to cow's milk had no significant effect on allergy. The 2020 review by Da Silva and colleagues based on the same studies specified that early exposure to cooked hen's egg is likely to reduce the prevalence of egg allergy, whereas raw or pasteurised egg might not. Two of the studies found that most infants with egg allergy were already sensitised and allergic by enrolment at age 4–6 months, indicating the need for earlier application of preventive measures. In a 2021 randomised trial, Sakihara and colleagues concluded that cow's milk allergy at age 6 months was significantly reduced after daily exposure to cow's milk between ages 1 and 2 months.Five randomised controlled trials investigating skin protection as primary prevention of atopic dermatitis were identified, including previous findings from our PreventADALL study. Only one trial reported on food allergy and found no preventive effect of regular emollients applied during the first year of life.
Added value of this study
To our knowledge, no other study has investigated potential additive or synergistic effects of early food allergen introduction and regular emollients to prevent food allergy. The PreventADALL study provides evidence that food allergy at age 36 months might be prevented by the introduction of common foods from age 3 months. The study demonstrated that the food intervention was effective in a general cohort not selected on the basis of atopic risk, suggesting that early feeding of 63 infants might prevent food allergy in one child at age 36 months. In analysis of specific food allergies, the intervention was effective for peanut allergy. There were no safety issues, and breastfeeding rate at 6 months was not affected by early food introduction. Early regular use of skin emollients did not reduce food allergy at 36 months.
Implications of all the available evidence
Collectively, our findings and those of other large randomised controlled trials show that introduction of allergenic foods before age 4 months reduced food allergy in early childhood. Reduced allergy was also observed in the absence of screening for risk of atopic disease. Early complementary feeding seems to be safe and at present is likely to represent a feasible primary prevention strategy to reduce food allergy. We believe that there is sufficient evidence to suggest that food allergy can be prevented by recommending early introduction of allergenic food complementary to regular feeding from age 3 months.