Expecting Mothers' Study of Consumption or Avoidance of Peanut and Egg (ESCAPE) - PROJECT SUMMARY/ABSTRACT Whereas peanut (PN) allergy is the most common cause of fatal and near-fatal food-allergic reactions in older children and adults, egg and cow’s milk are the most common food triggers of anaphylaxis in infancy. Egg allergy is the most common childhood IgE-mediated food allergy with prevalence rates ranging from 1.3-1.6% in general population up to 20% in high-risk infants. Egg sensitization is a significant risk factor for PN allergy and early aeroallergen sensitization, which can lead to the “atopic march”. Black children are over-represented among children with egg allergy and asthma is more prevalent in children with allergy to egg than any other food. Only 50% develop tolerance to egg by school-age; PN allergy is rarely outgrown. There is a critical “window of opportunity” for the introduction of allergenic solids around 4-6 months in decreasing the risk of food allergy as shown in randomized controlled trials with egg and PN. However, 36% of infants were already sensitized to egg at enrollment and about 9% to PN, excluding them from early introduction; 20% infants were clinically allergic, even anaphylactic, on their first introduction of egg. To be more effective, primary prevention strategies must begin much earlier before sensitization is established, possibly even during pregnancy or breastfeeding. Prior studies are conflicting in the effect of maternal diet including or excluding egg or PN on development of food allergy in infancy. Per the American Academy of Pediatrics, “Current evidence does not support a role for maternal dietary restrictions during pregnancy or lactation”, but randomized controlled trials are lacking. Thus, there is an urgent need to provide mothers with concrete advice on feeding practices based on good quality evidence. The overall objective of this application is to define the role for egg and PN exposure during pregnancy and via human milk in food sensitization and to identify the biomarkers of sensitization or tolerance. We will conduct a nationally-enrolled, randomized controlled, four-arm parallel trial. Mothers pregnant with infants at high risk (with first degree relative with an atopic disease) who intend to breastfeed >3 months will be enrolled utilizing social media and referrals and randomized to either consumption or avoidance of egg and PN containing foods throughout pregnancy and lactation to assess the risk of sensitization to egg and PN at 4 months before introduction of solid foods. In Aim 1, we will determine the effect of maternal dietary egg and PN avoidance during pregnancy and lactation on the risk of egg and PN sensitization in high-risk infants. In Aim 2, we will assess the level of infant oral and environmental exposure to egg and PN. In Aim 3, we will identify the immune responses elicited by maternal diet including or excluding egg and PN during pregnancy and lactation. Knowledge gained from these studies will uncover mechanisms of early-life sensitization necessary to establish maternal dietary guidelines in prevention of food allergy and the atopic march. 1