Colostrum and Mature Human Milk of Women from London, Moscow, and Verona: Determinants of Immune Composition

Abstract

Cytokines and growth factors in colostrum and mature milk may play an important role in infant immune maturation, and may vary significantly between populations. We aimed to examine associations between environmental and maternal factors, and human milk (HM) cytokine and growth factor levels. We recruited 398 pregnant/lactating women in the United Kingdom, Russia, and Italy. Participants underwent skin prick testing, questionnaire interview, and colostrum and mature milk sampling. HM cytokine and growth factor levels were quantified by electro-chemiluminescence. We found significant geographical variation in growth factor levels, but no evidence of variation between sites in cytokine detectability. There was an inverse correlation between time of milk sampling and growth factor levels in colostrum for Hepatocyte Growth Factor (HGF) and TGFβ1 and TGFβ3, but not TGFβ2, and levels were significantly higher in colostrum than mature milk for all growth factors. The kinetics of decline were different for each growth factor. Cytokines were present at much lower levels than growth factors, and the decline over time was less consistent. HM growth factors and cytokine levels vary between populations for unknown reasons. Levels of HM mediators decline at different rates postpartum, and these findings suggest specific biological roles for HM growth factors and cytokines in early postnatal development.

Immune components of early breastmilk: Association with maternal factors and with reported food allergy in childhood

“…We also confirmed the absence of an association between maternal atopy and IgA or TGFβ concentrations. As observed when comparing colostrum from France, Brazil, and Australia, but in contrast to the data obtained on colostrum from UK, Russia, and Italy or from farm vs non‐farm mothers, we did not find any association between TGFβconcentrations and place of residence (Poitiers being considered more rural than Nancy). Finally, we did not confirm the association between TNFα and IL‐6 and C‐section, nor the lower IL‐1β concentrations in smoking mothers…”

“…Data for around 30 of the factors analyzed were not available to date, and our study provides new reference values. Data obtained for other factors were globally in agreement with published data obtained in colostrum, although some discrepancies were observed, for example, for TGFβ, IgG4, and CCL2 concentrations . These differences may stem from variations in methodologies and standards provided by different manufacturers that are not normalized using an international reference.…”

“…Despite the potential role of early BM in neonate immunity and intestinal homeostasis, there are currently very few studies analyzing its composition in immune and growth factors, with only a limited number of components analyzed . The impact of the concentrations of early BM components on child atopy or allergy has also been poorly analyzed .…”

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

“…Previous research linked a number of physiological and environmental factors with the changes of TGF‐β levels in HM. Stage of lactation and time of sample collection, circadian and seasonal variations, time prior to freezing and length of sample storage, differences in laboratory techniques, ethnicity, residency, maternal lifestyle, smoking, diet, infection as well as depression and anxiety were found to be a confounders and appear to impact TGF‐β concentrations, thus possibly impacting health outcome development. Very few studies collected sufficient information and accounted for the duration and exclusivity of breastfeeding.…”

Breastfeeding and the gut-brain axis: is there a role for melatonin?

“…A multitude of immune-associated factors can be present, and transferred, in human breast milk, including whole cells, cytokines, chemokines, immunoglobulins (Igs), lysozymes, lactoferrin, human milk oligosaccharides and microbiota, as well as prebiotic glycans and various growth factors (42,43). These breast milk-derived factors are important, due, in part, to their role in the infant's gastrointestinal and immune system development (44).…”