Early supplementation for cow's milk allergy prevention in breastfed infants in Poland (ESCAPE-PL): a protocol for randomised controlled trial.

introductionCurrent recommendations for early introduction of cow's milk proteins in infants who cannot be breastfed vary and are inconsistent due to a lack of clear evidence. We aim to assess whether early supplementation with various nutritional interventions, including cow's milk formula (CMF), amino acid formula (AAF), donor human milk (DHM) or high-pressure processed 'pascalised' DHM (DHM-P) is effective for the primary prevention of cow's milk allergy (CMA) in breastfed neonates. METHODS AND ANALYSIS: We will perform an open-label randomised, controlled, head-to-head trial with four parallel arms in three Polish study centres (Warsaw). 1000 healthy full-term newborns of mothers eager to exclusively breastfeed will be allocated to receive early supplementation with one of four nutritional interventions: CMF, AAF, DHM or DHM-P. All children will receive 10 mL of each intervention per day for the first 3 days of life; exclusive breastfeeding will be recommended. However, if any supplementation in addition to the breastfeeding is needed, the assigned nutritional intervention will be provided until 4 months of age. The primary outcome is a cumulative incidence of CMA confirmed by open oral food challenge at 4-6 months and 12 months of age. Secondary outcomes include an incidence of sensitisation to cow's milk protein; a total score in the Cow's Milk Related Symptom Score; the percentage of children with acquired tolerance to cow's milk, feeding difficulties and exclusively and predominantly breastfed; an incidence of atopic dermatitis, allergic rhinitis and wheezing; growth; compliance and adverse events. The level of immunomodulatory factors in maternal milk and its nutritional component analysis will also be performed. ETHICS AND DISSEMINATION: The ethics committee of the Medical University of Warsaw, Poland, approved this protocol (KB/61/2023). The results of this study will be submitted to a peer-reviewed journal no later than 1 year after data collection. The abstract will be presented at relevant national and international conferences. TRIAL REGISTRATION NUMBER: NCT06652698.