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, 173 (12), 1137-1145
[Online ahead of print]

Primary Prevention of Cow's Milk Sensitization and Food Allergy by Avoiding Supplementation With Cow's Milk Formula at Birth: A Randomized Clinical Trial


Primary Prevention of Cow's Milk Sensitization and Food Allergy by Avoiding Supplementation With Cow's Milk Formula at Birth: A Randomized Clinical Trial

Mitsuyoshi Urashima et al. JAMA Pediatr.


Importance: Cow's milk formula (CMF) is used to supplement breastfeeding (BF) at birth without clear clinical evidence to support the practice.

Objective: To determine whether avoiding supplementation with CMF at birth can decrease risks of sensitization to cow's milk protein and/or clinical food allergy, including cow's milk allergy (CMA), overall and in subgroups stratified by 25-hydroxyvitamin D (25[OH]D) levels.

Design, setting, and participants: The Atopy Induced by Breastfeeding or Cow's Milk Formula (ABC) trial, a randomized, nonblinded clinical trial, began enrollment October 1, 2013, and completed follow-up May 31, 2018, at a single university hospital in Japan. Participants included 330 newborns at risk for atopy; of these, 312 were included in the analysis. Data were analyzed from September 1 through October 31, 2018.

Interventions: Immediately after birth, newborns were randomized (1:1 ratio) to BF with or without amino acid-based elemental formula (EF) for at least the first 3 days of life (BF/EF group) or BF supplemented with CMF (≥5 mL/d) from the first day of life to 5 months of age (BF plus CMF group).

Main outcomes and measures: The primary outcome was sensitization to cow's milk (IgE level, ≥0.35 allergen units [UA]/mL) at the infant's second birthday. Secondary outcomes were immediate and anaphylactic types of food allergy, including CMA, diagnosed by oral food challenge test or triggered by food ingestion, with food-specific IgE levels of at least 0.35 UA/mL. Subgroup analysis was prespecified by tertiles of serum 25(OH)D levels at 5 months of age.

Results: Of the 312 infants included in the analysis (160 female [51.3%] and 152 male [48.7%]), 151 of 156 (96.8%) in the BF/EF and BF plus CMF groups were followed up until their second birthday. The primary outcome occurred in 24 infants (16.8%) in the BF/EF group, which was significantly fewer than the 46 infants (32.2%) in the BF plus CMF group (relative risk [RR], 0.52; 95% CI, 0.34-0.81). The middle tertile of the 25(OH)D subgroup, but not the low and high tertiles, had a significant interaction with the intervention (RR, 0.19; 95% CI, 0.07-0.50; P = .02). The prevalence of food allergy at the second birthday was significantly lower in the BF/EF than in the BF plus CMF groups for immediate (4 [2.6%] vs 20 [13.2%]; RR, 0.20; 95% CI, 0.07-0.57) and anaphylactic (1 [0.7%] vs 13 [8.6%]; RR, 0.08; 95% CI, 0.01-0.58) types.

Conclusions and relevance: The evidence suggests that sensitization to cow's milk and food allergy, including CMA and anaphylaxis, are primarily preventable by avoiding CMF supplementation for at least the first 3 days of life.

Trial registration: Identifier: UMIN000011577.

Conflict of interest statement

Conflict of Interest Disclosures: Dr M. Urashima reported receiving grants from the Ministry of Education, Culture, Sports, Science, and Technology in the Japan-Supported Program for the Strategic Research Foundation at Private Universities, grant JP16K09074 from the Japanese Society for the Promotion of Science Grants-in-Aid for Scientific Research, grant 15ek0410019h0101 from the Practical Research Project for Allergic Disease and Immunology of the Japan Agency for Medical Research and Development, grants from Dairy Products Health Science Council and Japan Dairy Association, and grants from the Jikei University School of Medicine during the conduct of the study. No other disclosures were reported.

Comment in

  • JAMA Pediatr. doi: 10.1001/jamapediatrics.2019.3560

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