Primary Prevention of Cow’s Milk Allergy

A recent randomized clinical study (M Urashima et al. JAMA Pediatr. 2019;173(12):1137-1145) indicates that avoiding cow’s milk formula in the first 3 days of life may prevent the development of cow’s milk allergy. Thanks to Ben Gold for this reference.

Link to full Abstract (article behind paywall): Primary Prevention of Cow’s Milk Sensitization and Food Allergy by Avoiding Supplementation With Cow’s Milk Formula at Birth

The Atopy Induced by Breastfeeding or Cow’s Milk Formula (ABC) trial, a randomized, nonblinded clinical trial, began enrollment October 1, 2013, and completed follow-up May 31, 2018, at a single university hospital in Japan. The primary outcome was sensitization to cow’s milk (IgE level, ≥0.35 allergen units [UA]/mL) at the infant’s second birthday.

Immediately after birth, newborns were randomized (1:1 ratio) to BF with or without amino acid–based elemental formula (EF) for at least the first 3 days of life (BF/EF group) or BF supplemented with CMF (≥5 mL/d) from the first day of life to 5 months of age (BF plus CMF group).

If the mother, allocated to the BF/EF group, added more than 150 mL/d of EF to BF for 3 consecutive days, EF was switched to CMF after the fourth day. Thus, offspring allocated to BF/EF could avoid CMF for at least the first 3 days of life.

Key Finding:

  • “In this randomized clinical trial involving 312 newborns, risks of sensitization to cow’s milk and immediate-type food allergy, including cow’s milk allergy and anaphylaxis, were decreased by avoiding supplementation with cow’s milk formula for at least the first 3 days of life.”
  • “The primary outcome occurred in 24 infants (16.8%) in the BF/EF group, which was significantly fewer than the 46 infants (32.2%) in the BF plus CMF group (relative risk [RR], 0.52; 95% CI, 0.34-0.81).”
  • “The prevalence of food allergy at the second birthday was significantly lower in the BF/EF than in the BF plus CMF groups for immediate (4 [2.6%] vs 20 [13.2%]; RR, 0.20; 95% CI, 0.07-0.57) and anaphylactic (1 [0.7%] vs 13 [8.6%]; RR, 0.08; 95% CI, 0.01-0.58) types.”

This study is interesting in that it suggests that exposure to cow’s milk in the first three days of life potentially increases the risk of CMA, whereas a previous study (*see below) showed showed that early exposure to CMF within 14 days after birth reduces the risk of CMA.  In this previous study, exposure to small quantities of CMF for the first 3 days of life was not monitored. “Thus, the results of that observational study are not necessarily in contrast to those of the present trial.”

My take: This type of study is difficult to complete.  It is difficult to understand why exposure to cow’s milk in the first two weeks of life is helpful and why exposure in the first three days of life is detrimental with regard to the development of cow’s milk allergy.

*Katz Y, Rajuan N, Goldberg MR, et al. Early exposure to cow’s milk protein is protective against IgE-mediated cow’s milk protein allergy. J Allergy Clin Immunol. 2010;126(1):77-82.e1. doi:10.1016/j.jaci.2010.04.020)

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Limiting Cow’s Milk for EoE

A small retrospective study suggests that eliminating cow’s milk, without other interventions, can be effective in the treatment of Eosinophilic Esophagitis (EoE) (JPGN 2012; 55: 711-16).

Out of 161 children with EoE, 17 patients were identified who excluded only cow’s milk from their diet.  Remission was noted in 65%.  Complete histologic remission (≤1 eosinophil/hpf) was noted in 7 patients (41%) and 4 (24%) had “significant remission” (defined as peak eosinophil count of 2-15/hpf).

This study, conducted in Chicago, took place between 2006-2011.  The majority of the patients treated at this institution are treated with dietary elimination: 61% with empiric elimination diet, 8% empiric elimination diet with topical steroids, and 7% with elemental diet.

The authors suggested that younger children may be more likely to benefit from this approach but cautioned against drawing firm conclusions due to the small ‘scope’ of this retrospective study.

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More intriguing than helpful

A recent study reports that a pH-impedance (pH-MII) may help identify children with allergen-induced gastroesophageal reflux disease (GERD) after exposure to cow’s milk (J Pediatr 2012; 161: 476-81).  The study population included 17 children (average age 14 months) with a clinical diagnosis of cow’s milk allergy (CMA) who had responded to an elemental diet.

Given the limitations of the study, it is hard to take seriously the conclusions of the authors that in “selected cases of children with CMA in whom GERD is suspected” pH-MII “should be considered as part of diagnostic workup.”

The limitations:

  • CMA diagnosed clinically based on response to dietary therapy
  • GERD diagnosed based on Infant GER Questionnaire, though authors acknowledge that “we are aware that no symptom or cluster of symptoms have been shown to reliably predict the diagnosis of GERD”
  • Statistically-significant findings only for weakly acidic reflux which was induced on second day after switching from elemental formula to cow’s milk
  • No endoscopic correlation of mucosal disease or exclusion of eosinophilic esophagitis
  • Small number of patients

I cannot see how obtaining a pH-MII study would offer a meaningful benefit to these patients; though, it is intriguing that one potential measure of clinical deterioration like increased weakly acid episodes can be detected when these patients are challenged with cow’s milk.

Some related blog entries:

Impedance recommendations from PIG

Gastroesophageal Reflux: I know it when I see it

Guidelines for Eosinophilic Esophagitis