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    Single dose challenges in the diagnosis and management of cow's milk allergy in infants
    (University College Cork, 2021-06-28) d'Art, Yvonne; Hourihane, Jonathan O'B.; Gibson, Louise; Byrne, Aideen; National Children's Research Centre
    Background: Cows milk protein allergy (CMPA) is one of the most common food allergies in infancy. While it usually resolves slowly over time in most cases, it significantly disrupts family life and compromises affected childrens’ nutrition and growth. Parents often display significant anxiety about this condition and we speculated if this anxiety predates or develops in response to the onset of CMPA in their child. Single dose challenges are a new method of assessing dose reactivity in food allergic children. We recruited children referred for evaluation of CMPA to a randomised, controlled trial of single dose exposure to cows milk, using the validated dose of milk that would elicit reactions in 5% of CMPA subjects - the ED05, before implementation of graded exposure to CM (using the 12 step IMAP Milk Tolerance Induction Ladder) at home. Methods: 60 infants were recruited from referrals to 2 tertiary allergy centres and 1 secondary level allergy clinic. Inclusion criteria were age <12 months, a convincing CM allergic reaction <2 months before assessment and positive skin prick test (SPT) to milk +/- raised SpIgE to milk. Children were randomised 2:1 to a single dose of the ED05 for CM - (0.5mg milk protein) given as liquid CM (0.015mls) and observed for 2 hours post ingestion - or to no dose. Results: 60 patients were recruited, 57 (95%) were followed to 6 months, 3 intervention subjects were lost to follow up. 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 reached step 12 (ie drinking unheated cow’s milk) compared to 2/20 (10%) of the controls (p=0.049). 12 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 23/36(64%) of the intervention group were at step 12 compared to 7/19(37%) of the control group. Maternal state and trait anxiety 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 ED05 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.