Early Supplementation for Cow's Milk Allergy Prevention

Official title

Early Supplementation for Cow's Milk Allergy Prevention in Breastfed Infants in Poland (ESCAPE-PL): a Protocol for Randomised Controlled Trial

Overview

Cow's milk allergy (CMA) is a common food allergy in infants and young children that can have a significant impact on the individual and their family due to dietary restrictions, risk of nutritional deficiencies, social limitations, and decreased quality of life. It also represents a financial burden for families and healthcare resources. There is an ongoing debate about the significance of early exposure to cow's milk proteins within hours or days after birth and its relationship to the risk of developing CMA later in life. Current 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. This knowledge gap underscores the need for further research to provide a definitive understanding of the relationship between early exposure to cow's milk proteins and the development of CMA, which will ultimately inform evidence-based prevention strategies to improve the health and well-being of affected individuals and their families. This trial aims to investigate whether early supplementation with various nutritional interventions (cow's milk formula \[CMF\], amino acids formula \[AAF\], donor human milk \[DHM\], or high-pressure processed "pascalized" donor human milk \[DHM-P\]) could serve as an effective strategy for the primary prevention of CMA in breastfed neonates. This study is an open-label randomized, controlled, head-to-head trial with four parallel arms and allocation 1:1:1:1.

Interventions

• Other Cow's milk formula [CMF]
  At least 10 ml daily of cow's milk formula (Bebiko 1 NUTRIFlor Expert®, Nutricia; formula with galactooligosaccharides and without probiotics); and if additional supplementation will be needed (i.e., insufficient, partial, or discontinuation of breastfeeding), the randomly assigned nutritional intervention until the end of 4 months of age will be provided.
• Other Amino-acid formula [AAF]
  At least 10 ml daily of amino-acid formula (Nutramigen Pureamino®, Reckitt Benckiser Group PLC); and if additional supplementation will be needed (i.e., insufficient, partial, or discontinuation of breastfeeding), the randomly assigned nutritional intervention until the end of 4 months of age will be provided.
• Other Donor human milk [DHM]
  At least 10 ml daily of donor human milk; and if additional supplementation will be needed (i.e., insufficient, partial, or discontinuation of breastfeeding), the randomly assigned nutritional intervention until the end of 4 months of age will be provided.
• Other High-pressure processed "pascalized" donor human milk [DHM-P]
  At least 10 ml daily of high-pressure processed "pascalized" donor human milk; and if additional supplementation will be needed (i.e., insufficient, partial, or discontinuation of breastfeeding), the randomly assigned nutritional intervention until the end of 4 months of age will be provided.

Primary outcome measures

• A cumulative incidence of cow's milk allergy confirmed by open oral food challenge [Time frame: At 4-6 and 12 months of age]

Secondary outcome measures (12)

• A cumulative incidence of sensitization to cow's milk protein (cut-off levels for specific IgE level ≥0.35 allergen units [UA/mL] and ≥3 mm of wheal size in the skin prick test against cow's milk [Time frame: at 6 and 12 months of age]
• A point prevalence of cow's milk allergy confirmed by open oral food challenge [Time frame: at 4-6, and 12 months of age]
• An incidence of sensitization to cow's milk protein (cut-off levels for specific IgE level ≥0.35 allergen units [UA/mL] against cow's milk) [Time frame: at 4-6, and 12 months of age]
• In a subgroup of children with confirmed cow's milk allergy, the percentage of children with tolerance acquisition to cow's milk [Time frame: at 9 and/or 12 months]
• Percentage of children who received a full 3-day nutritional supplementation (3x10 ml according to the randomization) and then were exclusively or predominantly breastfed until 4 months of age [Time frame: Up to 4 month of age]
• A total score in the Cow's Milk-related Symptom Score (CoMiSS) [Time frame: at 4-6 and 12 months of age]
• Percentage of children exclusively breastfed [Time frame: at 4 and 6 months of age]
• Percentage of children with mixed feeding [Time frame: at 4 and 6 months of age]
• Change in Body Mass Index (BMI)-for-age z-score [Time frame: at 4, 6 and 12 months of age]
• Change in length-for-age z-score [Time frame: at 4, 6 and 12 months of age]
• Adverse events related to the nutritional intervention (according to the randomization) [Time frame: up to 12 months of age]
• A cumulative incidence of atopic dermatitis (defined as meeting the UK Working Party diagnostic Criteria) [Time frame: at 6 and 12 months of age]

Eligibility criteria

Inclusion criteria

• Healthy newborns of mothers who express the intention to exclusively breastfeed for first 6 months of infant's life
• Full-term infants (defined as gestational age of at least 37 weeks)
• Infant birth weight at least 2500 g and ≤ 4500 g
• Age at enrolment <24 h of life
• Regardless of any atopic condition in parents
• Written informed consent of the caregiver

Exclusion criteria

• Infants of parents who intend to partially or fully formula feed
• Serious congenital anomalies or any other medical condition that would preclude the consumption of any of the study formulas, or interfere with nutrition or growth
• Contradictions to exclusive breastfeeding
• Multiple pregnancy

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Poland · 1 center

• Medical University of Warsaw — Warsaw

Publications

• Horvath A, Wesolowska A, Strozyk A, Bzikowska-Jura A, Ambrozej D, Dumycz K, Feleszko W, Szajewska H. Early supplementation for cow's milk allergy prevention in breastfed infants in Poland (ESCAPE-PL): a protocol for randomised controlled trial. BMJ Open. 2025 Aug 5;15(8):e096217. doi: 10.1136/bmjopen-2024-096217. PMID 40764079

Identifiers

NCT: NCT06652698 · ABM30

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗