In neonates with vitamin D deficiency, low lymphocyte activation markers are risk factors for infection

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Abstract
Background: Vitamin D has regulatory effects on different cells of the immune system and low levels are associated with several immune-mediated diseases. Aim: To investigate the association between neonatal 25-hydroxy vitamin D (25-OHD) level and the expression of lymphocyte activation markers (HLA-DR, CD69, CD25, CD45RA) on T-lymphocyte subpopulations and its impact in neonatal infection. Methods: 25-OHD level was measured in the cord blood of 56 neonates and their mothers using an enzyme immune-assay method. Based on the 25-OHD level, infants were categorised into four groups: severe deficiency (n = 7), moderate deficiency (n = 21), mild deficiency (n = 15) and normal 25-OHD level (n = 13). Mothers were classified into deficient (n = 18), insufficient (n = 21) and normal levels (n = 17). T-lymphocyte subpopulations and lymphocyte activation markers were investigated using flow cytometry. Results: There was a positive correlation between maternal and cord blood 25-OHD levels (r = 0.503, p = 0.001). The group with severe 25-OHD deficiency had the significantly lowest level of total lymphocytes, CD3+ T lymphocytes, CD4+ T-helper and CD8+ T-cytotoxic lymphocytes and CD4+CD45RA+ naïve T-cells compared with the other groups. The frequencies of CD8+CD25+, CD4+CD25+ and CD4+HLA-DR+ activated T-lymphocytes were significantly lower in the severe, moderate and mild deficiency groups than in the normal group. Seven of 43 (16.27%) infants with 25-OHD deficiency were admitted with sepsis to the neonatal intensive care unit and there were no cases of sepsis in the normal 25-OHD group. Conclusion: Vitamin D deficiency is associated with a reduction of lymphocyte subsets and altered T-lymphocyte activation which are considered to be risk factors for neonatal infection.

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