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

Abstract

Previous research has produced conflicting evidence on the preventive effects of early introduction of cow's milk protein on cow's milk allergy (CMA). 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. 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. 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. Daily ingestion of CMF between 1 and 2 months of age prevents CMA development. This strategy does not compete with breast-feeding.