Cow's Milk Allergy, Food Allergy
Conditions
Brief summary
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
OTHERCow'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.
OTHERAmino-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.
OTHERDonor 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.
OTHERHigh-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.
Sponsors
Medical Research Agency, Poland
Medical University of Warsaw
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 24 Hours
Healthy volunteers
Yes
Inclusion criteria
1. Healthy newborns of mothers who express the intention to exclusively breastfeed for first 6 months of infant's life 2. Full-term infants (defined as gestational age of at least 37 weeks) 3. Infant birth weight at least 2500 g and ≤ 4500 g 4. Age at enrolment \<24 h of life 5. Regardless of any atopic condition in parents 6. Written informed consent of the caregiver
Exclusion criteria
1. Infants of parents who intend to partially or fully formula feed 2. 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 3. Contradictions to exclusive breastfeeding 4. Multiple pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| A cumulative incidence of cow's milk allergy confirmed by open oral food challenge | At 4-6 and 12 months of age |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| A point prevalence of cow's milk allergy confirmed by open oral food challenge | 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) | 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 | at 9 and/or 12 months | Tolerance acquisition to cow's milk will be assessed by subsequent OFC with baked milk (in the form of biscuit or muffin); if baked milk is tolerated, the assessment of tolerance acquisition will be continued with the use of milk ladder. |
| 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 | Up to 4 month of age | — |
| A total score in the Cow's Milk-related Symptom Score (CoMiSS) | at 4-6 and 12 months of age | The total CoMiSS score ranges from 0 to 33, a score of ≥10 indicates CMA. |
| Percentage of children exclusively breastfed | at 4 and 6 months of age | — |
| Percentage of children with mixed feeding | at 4 and 6 months of age | — |
| Change in Body Mass Index (BMI)-for-age z-score | at 4, 6 and 12 months of age | weight and length will be checked each month in a telephone interview or parental report, or during follow-up visit assessed by study physician; change in mean value will be assessed between baseline and each time point |
| Change in length-for-age z-score | at 4, 6 and 12 months of age | length will be checked each month in a telephone interview or parental report, or during follow-up visit assessed by study physician; change in mean value will be assessed between baseline and each time point |
| Adverse events related to the nutritional intervention (according to the randomization) | up to 12 months of age | defined as any harmful events that may occur during the trial; the process of decision whether an adverse event is related to the intervention (attribution) will be made by the non-blinded principal investigator |
| 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 | at 6 and 12 months of age | — |
| A cumulative incidence of allergic rhinitis (confirmed by study physician) | at 6 and 12 months of age | — |
| A cumulative incidence of feeding difficulties who will be screened with The Montreal Children's Hospital Feeding Scale (MCH-FS scale) | at 6 and 12 months of age | Total score range from 14 to 98, score of 46 or higher indicates feeding difficulties. |
| Human milk energy value (kcal/100 mL) | at 4-14 days postpartum and 6 months of age | — |
| Total and true protein concentrations in human milk samples (g/100 mL) | at 4-14 days postpartum and 6 months of age | — |
| Fat concentration in human milk samples (g/100 mL) | at 4-14 days postpartum and 6 months of age | — |
| Lactose concentration in human milk samples (g/100 mL) | at 4-14 days postpartum and 6 months of age | — |
| Dry mass content g/100 mL | at 4-14 days postpartum and 6 months of age | — |
| IgA-anty CMA concentration in human milk samples (pg/mL) | at 4-14 days postpartum | — |
| IL-1B, IL-6, IL-10, and TGF-beta concentrations in human milk samples (pg/mL) | at 4-14 days postpartum | — |
| A cumulative incidence of atopic dermatitis (defined as meeting the UK Working Party diagnostic Criteria) | at 6 and 12 months of age | — |
Countries
Poland
Contacts
Primary ContactAndrea Horvath, Assoc Prof
Outcome results
None listed