Transforming growth factor beta in human milk and allergic outcomes in children: A systematic review

Ekaterina Khaleva; Zoya Gridneva; Donna T Geddes; Wendy H Oddy; Silvia Colicino; Oleg Blyuss; Robert J Boyle; John O Warner; Daniel Munblit

doi:10.1111/cea.13409

Transforming growth factor beta in human milk and allergic outcomes in children: A systematic review

Clin Exp Allergy. 2019 Sep;49(9):1201-1213. doi: 10.1111/cea.13409. Epub 2019 Jun 2.

Authors

Ekaterina Khaleva^{1

2}, Zoya Gridneva^{2

3}, Donna T Geddes^{2

3}, Wendy H Oddy⁴, Silvia Colicino⁵, Oleg Blyuss^{6

7

8}, Robert J Boyle^{2

9

10}, John O Warner^{2

9

11}, Daniel Munblit^{2

8

9

12}

Affiliations

¹ University of Southampton, Southampton, UK.
² inVIVO Planetary Health, Research Group of the Worldwide Universities Network, West New York, New Jersey.
³ School of Molecular Sciences, The University of Western Australia, Perth, Western Australia, Australia.
⁴ Nutritional Epidemiology, Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
⁵ The National Heart and Lung Institute, Imperial College London, London, UK.
⁶ Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
⁷ Department of Applied Mathematics, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia.
⁸ Department of Pediatrics, Faculty of Pediatrics, Sechenov University, Moscow, Russia.
⁹ Department of Paediatrics, Imperial College London, London, UK.
¹⁰ Centre of Evidence-based Dermatology, University of Nottingham, Nottingham, UK.
¹¹ Paediatrics and NIHR Collaboration for Leadership in Applied Health Research and Care for NW London, London, UK.
¹² Healthcare Department of Moscow, Moscow Research and Clinical Center for Neuropsychiatry, Moscow, Russia.

PMID: 31058363
DOI: 10.1111/cea.13409

Abstract

Background: Human milk (HM) transforming growth factor beta (TGF-β) is critical for inflammation regulation and oral tolerance promotion. Previous reports suggested that variations in HM TGF-β levels are associated with allergic outcomes.

Objective: We undertook a systematic review (PROSPERO 2017 CRD42017069920) to reassess the evidence on the relationships between HM TGF-β and allergic outcomes in children.

Methods: Electronic bibliographic databases (MEDLINE, EMBASE and Cochrane Library) were systematically searched. Two independent reviewers screened reference lists, extracted the data and assessed risk of bias using the National Institute for Clinical Excellence methodological checklist.

Results: A total of 21 studies were identified. Sixteen studies assessed relationships between HM TGF-β and risk of eczema; 14, allergic sensitization; nine, wheezing/asthma; six, food allergy; three, allergic rhinitis/conjunctivitis. Five cohorts (5/18, 28%) reported a protective effect of TGF-β1, while 3 (3/10, 30%) suggested increased risk of allergic outcomes development and 1 (1/10, 10%), a protective effect of TGF-β2 on eczema. Meta-analysis was not possible due to significant heterogeneity in methodology, age of outcome assessment and differing statistical approaches. 71% (15/21) of studies carried a high risk of bias.

Conclusion and clinical relevance: In contrast with previous findings, we did not find strong evidence of associations between HM TGF-β and allergic outcomes. Differences in studies' methodology and outcomes do not allow unconditional rejection or acceptance of the hypothesis that HM TGF-β influences the risk of allergy development. Future studies on diverse populations employing standardized methods, accurate phenotyping of outcomes and evaluation of the effect of TGF-β in combination with other HM immune markers, microbiome and oligosaccharides are required.

Keywords: allergic diseases; allergic sensitization; allergy; atopy; breast milk; breastfeeding; colostrum; human milk; transforming growth factor beta.

Publication types

Systematic Review

MeSH terms

Female
Humans
Infant
Infant, Newborn
Male
Milk Hypersensitivity / immunology*
Milk Hypersensitivity / pathology
Milk Proteins / immunology*
Milk, Human / immunology*
Transforming Growth Factor beta1 / immunology*
Transforming Growth Factor beta2 / immunology*

Substances

Milk Proteins
TGFB1 protein, human
TGFB2 protein, human
Transforming Growth Factor beta1
Transforming Growth Factor beta2