Timing of Cow’s Milk Protein Introduction and Childhood Adverse Reactions to Cow’s Milk

To examine the relationship between cow’s milk protein introduction (CMPI) timing and the occurrence of cow’s milk adverse reactions (CMAR) in childhood, considering potential interactions regarding formula supplementation immediately after birth.

The study examined 1298 mother-child pairs from Project Viva, a prospective prebirth cohort study, who had data available regarding the timing of CMPI and the presence or absence of cow’s milk allergy, intolerance, or sensitivity. The study excluded one child with galactosemia. The remaining participants were tracked from delivery to early adolescence via in-person research visits.

This is a population-based cohort study in the Boston, Massachusetts area. Questionnaires administered at different stages of childhood assessed the timing of CMPI (<2 weeks, 2 weeks to <6 months, ≥6 months), CMAR, cow’s milk sensitization, and cow’s milk allergy. Multivariable logistic regression models were used, accounting for parental atopy history, delivery mode, gestational age at delivery, child race, and median household. Impact modification by breastfeeding status and postdelivery hospital formula supplementation were also examined.

Of the participants, 32% of children were introduced to cow’s milk protein within the first 2 weeks after birth, 38% between 2 weeks and 6 months, and 30% at 6 months or later. Children introduced to cow’s milk at 6 months or later had over twice the risk of CMAR between ages 2 and 13 years compared with those introduced before 2 weeks (odds ratio, 2.1; 95% confidence interval, 1.2–3.7). Children with early CMPI (<2 weeks) who did not receive a formula supplement at delivery had a 4 times higher predicted probability of early childhood CMAR than children with early CMPI who did receive a formula supplement (adjusted odds ratio of 5.1 [95% confidence interval, 1.6–16.2]). Children who were administered formula postdelivery with early CMPI exhibited the lowest overall risk of CMAR. Timing of CMPI was not associated with either serum evidence of sensitization to milk or IgE-mediated milk allergy.

This study aligns with extant evidence suggesting the early introduction of cow’s milk protein is protective against cow’s milk adverse reactions later in childhood. Additionally, it is indicated that the ideal timing for CMPI may be contingent upon hospital formula supplementation postdelivery.

Cow’s milk allergy is among the most common food allergies observed in infants and young children. Despite current recommendations encouraging early introduction to potentially allergenic foods, there is a lack of well-established research regarding the optimal approaches for foods other than peanuts. This study is one of the first to assess optimal timing, amount, and exposure routes for CMAR mitigation. Further studies should be conducted in more diverse populations with different healthcare access to assess the generalizability of the results.