Avoiding cow’s milk formula (CMF) supplementation within the first 3 days of life may potentially reduce the risk of asthma and recurrent wheeze in young children, according to study results published in JAMA Network Open.

As part of a randomized clinical trial conducted in Japan (UMIN-CTR Clinical Trial Identifier: UMIN000011577), 312 newborns were randomly assigned to either a breast feeding (BF) group with or without amino acid-based elemental formula (EF) and avoiding CMF for the first 3 days of life (n=156), or a BF supplemented group with a small amount of CMF (≥5 mL/d) from the first day of life (n=156).  

A total of 302 participants (n=151 the CMF and no CMF groups) were followed up until their second birthday and were compared among 4 groups: no CMF without atopic conditions; no CMF with atopic conditions; CMF without atopic conditions; CMF with atopic conditions. Follow-up examinations for infants showing signs of atopy (eg, eczema, atopic dermatitis, food allergy, recurrent wheeze, and/or atopic sensitization) ended at 24 months and the assessment for risk of food allergy lasted until 2018 for all participants.


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During the follow-up period, atopy developed in 77 of the 151 infants (51.0%) in the no CMF group and required extended follow-up for a median of 3.0 years. Meanwhile, atopy developed in 81 of the 151 infants (53.6%) in the CMF group and underwent extended follow-up for a median of 3.3 years. The serum levels of 25-hydroxyvitamin D (25[OH]D), total immunoglobulin E (IgE), and antigen-specific IgE levels were measured at age 5 months and 24 months.

Researchers diagnosed asthma or recurrent wheeze in 42 of 302 participants (13.9%) at a median of 2.8 years of age. Asthma or recurrent wheeze developed in 15 of the 151 infants in the no CMF group, which was considerably less than the CMF group (27 of 151 infants; risk difference [RD], -0.079; 95% CI, -0.157 to -0.002; risk ratio [RR], 0.556; 95% CI, 0.308-1.002). In the subgroups of infants with atopic conditions at age 2 years and continued follow-up through age 6 years, 19.5% (15 of 77) of infants were diagnosed with asthma or recurrent wheeze in the no CMF group and 33.3% (27 of 81) of infants in the CMF group (RD, -0.139; 95% CI, -0.274 to -0.003; RR, 0.584; 95% CI, 0.338-1.012).

In children with 25(OH)D levels above the median at age 5 months, asthma or recurrent wheeze developed in 6.4% (5 of 78) in the no CMF group vs 24.6% (17 of 69) in the CMF group (RD, -0.182; 95% CI -0.298 to -0.067; P for interaction =.04). However, in the subgroup with lower 25(OH) D levels, avoiding CMF did not significantly reduce the incidence of asthma or recurrent wheeze (11.8% vs 11.5%; RD, 0.002; 95% CI, -0.102 to 0.107; RR, 1.020; 95% CI, 0.417-2.496).

In terms of IgE levels, there was no statistically significant interaction between IgE levels at age 5 months and avoiding CMF. However, in those infants with the highest quartile level of IgE at 24 months, avoiding CMF at birth significantly reduced asthma or recurrent wheeze (5.3% vs 43.8%, respectively; RD, -0.385; 95% CI, -0.571 to -0.199; RR, 0.120; 95% Ci, 0.030-0.490; P for interaction =.004). This trend did not persist in other quartiles of total IgE.

Study limitations included the location, which was conducted in a center in Japan in the central area of Tokyo, which may make the results irrelevant to other racial/ethnic groups with different food cultures and to those in a different socioeconomic status’ than the participants. In addition, the study population may be too small to accurately detect risks of asthma or recurrent wheeze.

“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,” the researchers concluded.

Reference

Tachimoto H, Imanari E, Mezawa H, et al. 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. JAMA Netw Open. 2020;3(10):e2018534. doi:10.1001/jamanetworkopen.2020.18534