Single Dose Oral Food Challenge at Diagnosis Accelerates Cows Milk Allergic Infants’ Acquisition of Oral Tolerance to Milk, But Progress is Influenced by Maternal Anxiety

Background: Cow’s milk protein allergy (CMPA) is one of the most common food allergies in infancy. Parents often display significant anxiety about this condition. Single dose challenges are a new method of assessing dose reactivity in food allergic children. Methods: We recruited children referred for evaluation of CMPA to a randomised, controlled trial of single dose challenge to cow’s milk, using the validated dose of milk that would elicit reactions in 5% of CMPA subjects - the ED 05 - before implementation of graded exposure to CM (using the 12 step iMAP Milk Tolerance Induction Ladder) at home. Parents completed food allergy quality of life and State and Trait Anxiety Inventories (STAI). Results: Sixty patients were recruited, 57 (95%) were followed to 6 months. By 6 months 27/37 (73%) intervention subjects had reached step 6 or above on the milk ladder compared to 10/20 (50%) control subjects (p=0.048). By 6 months 11/37 (30%) intervention subjects had reached step 12 (ie drinking unheated cow’s milk) compared to 2/20 (10%) of the controls (p=0.049). Twelve months post randomisation 31/36(86%) of the intervention group and 15/19(79%) of the control group were on step 6 or above. However, 24/37 (65%) of the intervention group were at step 12 compared to 7/20 (35%) of the control group (p=0.03). Maternal STAIs were significantly associated with their infants’ response/progress on the milk ladder and with changes in skin prick test and spIgE levels at 6 and 12 months. Conclusion: Using the 12 step iMAP milk ladder accelerates natural tolerance induction in infants under 12 months with CMPA. A supervised single dose at the ED 05 significantly accelerates this further, probably by giving parents the confidence to proceed. Maternal anxiety generally reflects infants’ progress towards tolerance but preexisting high levels of maternal anxiety are associated with poorer progress. Funding: YD was in receipt of a Clinical Research Fellowship from the National Childrens Research Centre Ireland. Declaration of Interest: AM received research funding from Aimmune Therapeutics, RvR declares consultancies for HAL Allergy BV, Citeq BV, Angany Inc, speaker fees from HAL Allergy BV, ThermoFisher Scientific, ALK and stock options from Angany Inc. ADG receives research funding and speaker fees from Aimmune Therapeutics JO’BH receives research funding, speaker fees and consultancy fees from Aimmune Thereputics, research funding and speaker fees from DBV Technologies, research funding from Johnson&Johnson, Clemens von Pirquet Foundation and Temple st Hospital Research Foundation. Ethical Approval: Ethical approval was obtained from the Clinical Research Ethics Committees of the Cork Teaching Hospitals and Crumlin Hospital. Approval was granted on 26th September 2017.