Abstract

A growing number of studies are focusing on the associations between human milk (HM) immunological composition and allergic diseases. This scoping review aims to identify statistical methods applied in the field and highlight pitfalls and unmet needs. A comprehensive literature search in MEDLINE and Embase retrieved 13,607 unique records. Following title/abstract screening, 29 studies met the selection criteria and were included in this review. We found that definitions of colostrum and mature milk varied across the studies. A total of 17 out of 29 (59%) studies collected samples longitudinally, but only 12% of these used serial (longitudinal) analyses. Multivariable analysis was used in 45% of the studies, but statistical approaches to modelling varied largely across the studies. Types of variables included as potential confounding factors differed considerably between models. Discrimination analysis was absent from all studies and only a single study reported classification measures. Outcomes of this scoping review highlight lack of standardization, both in data collection and handling, which remains one of the main challenges in the field. Improved standardization could be obtained by a consensus group of researchers and clinicians that could recommend appropriate methods to be applied in future prospective studies, as well as already existing datasets.

Highlights

  • The prevalence of allergic disease has been rising worldwide in the past decades [1]

  • In the process of conducting the systematic reviews mentioned in the previous section, an extensive electronic search was performed in the bibliographic databases MEDLINE and Embase using both thesaurus and free-text terms to identify bibliographic records involving human milk (HM) and immunological composition, such as cytokines, chemokines and immunoglobulins

  • In agreement with the study by Silberzahn et al [18], we found that different groups tend to choose very different statistical methods for assessing the relationship between HM immune active molecules and allergic outcomes

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Summary

Introduction

The prevalence of allergic disease has been rising worldwide in the past decades [1]. This pattern is evident in westernised and urbanised countries [2], but recent data suggest that it is an emerging problem in the developing world [3]. “The Hygiene Hypothesis” has been proposed as the main theory to explain the increase in prevalence of allergic disease [4], pointing at a reduced repertoire of specific immunological responses to different organisms due to reduced stimulation of the immune system by microbial antigens associated with modern living. Human breast milk is a known contributor to neonatal infection prevention and recent data show that it may reduce the risk of non-communicable diseases. Some biologically active components in HM are suspected to be modified by interventions in the maternal diet and lifestyle during late pregnancy and lactation [9,10], subsequently influencing infant health outcomes [11,12]

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