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Probiotics for cow’s milk protein allergy: a systematic review of randomized controlled trials

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Abstract

Cow’s milk protein allergy (CMPA) is the commonest food allergy in infancy and is associated with significant health burden. Given their immune modulatory properties, probiotics have been proposed as a strategy for management of CMPA. We aimed to systematically review efficacy and safety of probiotics in the management of CMPA. Databases PubMed, EMBASE, CINAHL, Cochrane Central Library, and Google scholar were searched in August 2018 for randomized controlled trials (RCT) of probiotic supplementation as an adjunct in the management of infants with suspected/proven CMPA. Primary outcomes were resolution of hematochezia and acquisition of tolerance to CMP at 6, 12, 24, and 36 months. Secondary outcomes included effect on allergic symptoms (SCORAD index), growth, gut microbiota, and adverse effects. A total of 10 RCTs (n = 845; probiotics, 422; control, 423) with low to unclear risk of bias were included. Meta-analysis showed probiotic supplementation was not associated with earlier resolution of hematochezia (n = 87; RR: 1.45 (95% CI: 0.96–2.18), p = 0.08; level of evidence (LOE), very low), in presumed CMPA. In confirmed CMPA, probiotics were associated with higher rate of acquisition of tolerance to CMP at the end of 3 years compared with placebo (N = 493; RR, 1.47; 95% CI, (1.17–1.84); p = 0.0009; LOE, low]. Meta-analysis was not possible for other outcomes. There were no probiotic related adverse effects.

Conclusion: Limited low-quality evidence indicates that probiotic supplementation may be associated with earlier acquisition of tolerance to CMP in children with CMPA. Large well-designed trials are essential to confirm these findings.

What is Known:

• Cow’s milk protein allergy (CMPA) is one of the commonest food allergies in children. CMPA is associated with significant socioeconomic burden.

• Elimination diet and extensively hydrolyzed formula is the mainstay of the management of CMPA.

What is New:

• This first systematic review of randomized controlled trials shows that probiotics as an adjuvant can lead to earlier acquisition of tolerance to CMP in children at 36 months of age. However, the evidence is low quality and influenced by data from one large study.

• Probiotic supplementation was not associated with earlier resolution of hematochezia.

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Abbreviations

AAF:

Amino acid-based formula

CMPA:

Cow’s milk protein allergy

DBPCFC:

Double-blind placebo-controlled food challenge

IgE:

Immunoglobulin E

LGG:

Lactobacillus rhamnosus GG

RCT:

Randomized controlled trial

SCORAD:

Symptomatic improvement as per severity scoring of atopic dermatitis

PRISMA:

Preferred reporting items for systematic reviews and meta-analyses

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Acknowledgments

We would like to acknowledge Dr. Roberto Canani for sharing the data for review.

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Authors and Affiliations

  1. Department of Neonatal Paediatrics, King Edward Memorial Hospital, Perth, WA, Australia

    Sheeba Qamer & Sanjay Patole

  2. Department of Neonatalogy, Fiona Stanley Hospital, 11 Robin warren drive, Perth, WA, 6150, Australia

    Mangesh Deshmukh

  3. Department of Neonatalogy, St. John of God Hospital, Subiaco, Perth, WA, 6008, Australia

    Mangesh Deshmukh

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  1. Sheeba Qamer
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Contributions

Dr Qamer (SQ): Independent literature search, collected data, interpretation of data, writing the first and final draft of the manuscript.

Dr Deshmukh (MD): Independent literature search, coordinated and supervised data collection, handling meta-analysis software, carried out the initial analyses and help in writing the first and final draft of the manuscript. Addressing reviewers’ comments.

Dr Patole (SP): Conceptualized and designed the study, independent literature search, interpretation of the data, critically reviewed the manuscript for important intellectual content. Addressing reviewers’ comments.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Mangesh Deshmukh.

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Communicated by Nicole Ritz

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Qamer, S., Deshmukh, M. & Patole, S. Probiotics for cow’s milk protein allergy: a systematic review of randomized controlled trials. Eur J Pediatr 178, 1139–1149 (2019). https://doi.org/10.1007/s00431-019-03397-6

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