Breastfeeding and circulating immunological markers during the first 3 years of life: the DIABIMMUNE study

AIMS/HYPOTHESIS: Our aim was to study the association between duration of breastfeeding and circulating immunological markers during the first 3 years of life in children with HLA-conferred susceptibility to type 1 diabetes. METHODS: We performed a longitudinal analysis of 38 circulating immunological markers (cytokines, chemokines and growth factors) in serum samples from Finnish (56 individuals, 147 samples), Estonian (56 individuals 148 samples) and Russian Karelian children (62 individuals, 149 samples) at 3, 6, 12, 18, 24 and 36 months of age. We also analysed gut inflammation markers (calprotectin and human β defensin-2) at 3 (n = 96) and 6 months (n = 153) of age. Comparisons of immunological marker medians were performed between children who were breastfed for 6 months or longer vs children who were breastfed for less than 6 months. RESULTS: Breastfeeding for 6 months or longer vs less than 6 months was associated with lower median of serum immunological markers at 6 months (granulocyte-macrophage colony-stimulating factor [GMCSF], macrophage inflammatory protein [MIP-3α]), 12 months (IFN-α2, vascular endothelial growth factor, GMCSF, IFN-γ, IL-21), 18 months (FGF-2, IFN-α2) and 24 months of age (CCL11 [eotaxin], monocyte chemoattractant protein-1, TGFα, soluble CD40 ligand, IL-13, IL-21, IL-5, MIP-1α) (all p < 0.01) but not at 36 months of age. Breastfeeding was not associated with gut inflammation markers at 3 and 6 months of age. CONCLUSIONS/INTERPRETATION: Children who were breastfed for 6 months or longer had lower medians for 14 immunological markers at one or more age points during the first 2 years of life compared with children who were breastfed for less than 6 months. The clinical meaning of the findings is not clear. However, the present study contributes to the understanding of immunological differences in children that have been breastfed longer, and thus provides a mechanistic suggestion for the previously observed associations between breastfeeding and risk of type 1 diabetes. GRAPHICAL ABSTRACT: [Image: see text]