Profiling Stool Cytokines and Microbiome of Infants With Non-IgE-mediated Cow's Milk Protein Allergy Could Explain Its Pathophysiology and be Used as a Non-invasive Diagnostic Method (Melina Study)

STUDY DESIGN

Study description:

This observational study will involve the analysis of clinical data, stool, urine and serum (if available) samples that will be collected from infants with suspected or confirmed non-IgE-mediated CMPA. Clinical data will be collected from the medical notes of the patients with the written consent of the parents/carers. Dirty and wet (stools and urine samples) nappies from infants with possible non-IgE-mediated CMPA before dairy exclusion at time of enrolment, will be collected during acute and recovery phase according to the following schedule:

visit 1: recruitment day (two stool samples on two consecutive bowel motions), ideally before introduction of dairy free diet; visit 2: end of week 1; visit 3: end of week 4; visit 4: week 5, challenge to Cow's Milk Proteins (CMP) (two stool samples on two consecutive bowel motions, 6 hours up to 24 hours post challenge); visit 5: within a week post CMP challenge; visit 6: week 6. Samples from infants with possible non-IgE-mediated CMPA while on dairy free diet at enrolment will be collected at baseline (2 samples on 2 consecutive bowel motions), week 1, week 4 and week 6. If these patients are challenged to CMP within the 6 weeks of the study, faecal and urine samples will also be collected before (last bowel movement before challenge) and after challenge to CMP (two stool samples on two consecutive bowel motions, 6 hours up to 24 hours post challenge). For the IgE-mediated CMPA infants and healthy participants, faecal and urine samples will only be collected at 3 time points: on recruitment day, on week 4 and on week 6.

Infants presenting to primary and secondary care within Greater Glasgow & Clyde health board with symptoms suggesting possible non-IgE-mediated CMPA will be treated according to the local non-IgE-mediated CMPA guideline (for the formula fed infants a hypoallergenic formula milk will be offered; extensively hydrolyzed (eHF) or amino acid (AAF) formula, based on severity of the symptoms and history, while those on breast milk the mother will be advised to go on a dairy free diet). As per local guidelines, after 4 weeks of elimination diet (cow's milk from infant's and mother's if breast fed), infants with mild to moderated non-IgE-mediated CMPA will be offered an unsupervised oral food challenge (OFC) at home under the guidance of the community dietitian while more severe cases (such as CMPIE) will be offered an OFC under physician's supervision. In case of a convincing history such as repeated exposure to the incriminated food eliciting repetitive vomiting and/or diarrhoea within 24h, without any other cause for symptoms and absence of symptoms after elimination of cow's milk, the OFC will be omitted. Confirmed cases (following positive challenge or convincing history) will return to the exclusion diet (a hypoallergenic formula milk or breastfeeding with mother's dairy free diet) as per local guideline.