Early Food Intervention and Skin Emollients to Prevent Food Allergy in Young Children (PreventADALL): Factorial, Multicentre, Cluster-Randomised Trial

To determine if early introduction of commonly allergenic foods and regular application of skin emollients starting at 3 months of age decreases risk of food allergy in childhood.

This study included 2397 newborn infants born at Oslo University Hospital and Ostfold Hospital Trust in Norway, and Karolinska University Hospital in Sweden. Inclusion criteria included healthy newborn infants from the general population with or without atopic risk with gestational age of at least 35 weeks. The study population was followed from birth to 36 months of age.

This study was a factorial, cluster-randomized controlled trial. The study population was randomized into 4 intervention groups: (1) no intervention, (2) skin intervention, (3) food intervention, and (4) combined skin and food intervention. Participants in the skin intervention group began skin emollient usage at least 4 times a week from 2 weeks of age. Participants in the food intervention group began sequential introduction of 4 commonly allergenic infant-safe food products derived from peanut, cow’s milk, wheat, and hen’s egg between 3 and 4 months of age. A taste of peanut butter on the tip of the mother’s finger was introduced first at the 3-month visit, followed by cow’s milk, porridge, and scrambled eggs at each subsequent week. Foods were administered in no more than 1 teaspoon increments at least 4 times a week, complementary to regular feeding with breast milk or formula. For all intervention groups, clinical follow-up visits were conducted at 3, 6, 12, 24, and 36 months of age. Weekly electronic questionnaires were completed by parents to track adherence to interventions, possible food reactions, or development of eczema. At the final follow-up visit, a structured parental interview was conducted regarding food exposures and suspected food allergy, eczema, asthma, or rhinitis. A skin prick test was conducted to assess for allergic sensitization to foods and other common allergens. An expert panel classified children as having food allergy, probable food allergy, or no food allergy.

Exposure to commonly allergenic foods between the ages of 3 and 4 months, complementary to regular feeding, reduced food allergy at 36 months of age. Risk of food allergy was significantly lower in the food intervention group compared with the no intervention group (P < .004) and had a clinically significant number needed to treat of 63. There was no evidence that regular emollient use alone reduces the risk of food allergy. There was not enough data to support if combined food and skin intervention was more effective than food intervention alone. Breastfeeding rates remained high at 6 months of age across all study groups and were not affected by early introduction of food. There were no adverse outcomes.

Early introduction of commonly allergenic foods between 3 and 4 months of age is a safe, effective, affordable strategy to prevent food allergy in children and may decrease the burden of food allergy in a general population.

This study adds to the significant evidence that early introduction of infant-safe commonly allergenic foods is an effective food allergy prevention strategy that does not increase the development of food allergy and is feasible in children as young as 3 months of age. The dual allergen exposure hypothesis suggests that an impaired skin barrier (eg, eczema) before exposure to allergen in the gut is the likely medium via which allergen sensitization occurs; therefore, it has been hypothesized that emollient application could lead to food allergy prevention. Importantly, this study demonstrated that emollient application did not have any proven contribution to either food allergy prevention or development, and these authors previously reported that regular application of emollient early in life did not prevent the development of atopic dermatitis. The take-home message for primary care providers is to encourage introduction of infant-safe forms of commonly allergenic foods, especially peanut, as early as 3 months of age, reminding families to keep the food in the diet once introduced to prevent development of a potentially life-threatening food allergy.