Effect of Avoiding Cow's Milk Formula at Birth on Prevention of Asthma or Recurrent Wheeze Among Young Children: Extended Follow-up From the ABC Randomized Clinical Trial.

Importance: Children with food allergies may develop asthma or recurrent wheeze.

Objective: To evaluate whether asthma or recurrent wheeze among children were changed by avoiding supplementing breastfeeding (BF) with cow's milk formula (CMF) in the first 3 days of life.

Design, Setting, And Participants: This randomized, unmasked, clinical trial was conducted at 1 university hospital in Japan beginning October 2013 with follow-up examinations occurring until January 2020. A total of 312 newborns at risk for atopy were randomized and assigned to either BF with or without amino acid-based elemental formula (EF) or BF with CMF, with follow-up examinations for participants showing signs of atopy conducted at 24 months. Follow-up examinations ran through January 2020.

Interventions: Immediately after birth, newborns were randomly assigned (1:1 ratio) to either breastfeeding with or without amino acid-based elemental formula for at least the first 3 days of life (no CMF group) or breastfeeding supplemented with CMF (≥5 mL/d) from the first day of life to 5 months of age (CMF group).

Main Outcomes And Measures: Asthma or recurrent wheeze diagnosed by the pediatric allergy specialists of this trial; subgroups were stratified by serum levels of 25-hydroxyvitamin D and IgE.

Results: Of 312 infants (156 [50.0%] randomized to the no CMF group), 302 (96.8%) were followed up at their second birthday: 77 of 151 (51.0%) in the no CMF group and 81 of 151 (53.6%) in the CMF group underwent extended follow-up because of having atopic conditions. Asthma or recurrent wheeze developed in 15 (9.9%) of the children in the no CMF group, significantly less than the children in the CMF group (27 [17.9%]; risk difference, -0.079; 95% CI, -0.157 to -0.002). In participants with vitamin D levels above the median at 5 months of age, asthma or recurrent wheeze developled in 5 (6.4%) children in the no CMF group, significantly less than in the children in the CMF group (17 [24.6%]; risk difference, -0.182; 95% CI, -0.298 to -0.067; P for interaction = .04). In the highest quartile group of total IgE at age 24 months, asthma or recurrent wheeze developed in 2 children (5.3%) in the no CMF group, significantly less than the children in the CMF group (14 [43.8%]; risk difference, -0.385; 95% CI, -0.571 to -0.199; P for interaction = .004).

Conclusions And Relevance: The findings of this study suggest that avoiding CMF supplementation in the first 3 days of life has the potential to reduce the risk of asthma or recurrent wheeze in young children, especially among those with high vitamin D or high IgE levels.

Trial Registration: umin.ac.jp/ctr Identifier: UMIN000011577.