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

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: http://umin.ac.jp Identifier: UMIN000011577.