Randomized trial of early infant formula introduction to prevent cow's milk allergy

Background: Previous research has produced conflicting evidence on the preventive effects of early introduction of cow's milk protein on cow's milk allergy (CMA). Objective: Through a randomized controlled trial, we sought to determine whether the early introduction of cow's milk formula (CMF) could serve as an effective strategy in the primary prevention of CMA in a general population. Methods: We recruited newborns from 4 hospitals in Okinawa, Japan. Participants were randomly allocated to ingest at least10 mL of CMF daily (ingestion group) or avoid CMF (avoidance group) between 1 and 2 months of age. In the avoidance group breast-feeding was supplemented with soy formula as needed. Oral food challenge was performed at 6 months of age to assess CMA development. Continuous breast-feeding was recommended for both groups until 6 months of age Results: We identified 504 infants for randomization into the 2 groups. In all, the parents of 12 participants declined to receive the intervention, and the study sample comprised 491 participants (242 in the ingestion group and 249 in the avoidance group) for a modified intention-to-treat analysis. There were 2 CMA cases (0.8 %) among the 242 members of the ingestion group and 17 CMA cases (6.8 %) among the 249 participants in the avoidance group (risk ratio = 0.12; 95% CI = 0.01-0.50; P < .001). The risk difference was 6.0% (95% CI = 2.7-9.3). Approximately 70% of the participants in both groups were still being breast-fed at 6 months of age. Conclusions: Daily ingestion of CMF between 1 and 2 months of age prevents CMA development. This strategy does not compete with breast-feeding.