Circulating maternal concentrations of hormonally active vitamin D [calcitriol, 1,25(OH)2D] rise early in the first trimester, doubling by the end of the third trimester. The early rise in calcitriol is believed to be necessary for enabling the immunological adaptation by the mother required for the maintenance of a normal pregnancy. This immunological adaptation is characterized by downregulation of the T helper type 1 (Th1) cytokine responses and a shift towards domination by the Th2 type responses. Attenuation of the Th1-mediated immune response is one of the influences of calcitriol on regulatory T cell activity and dendritic cell maturation. There is accumulating evidence that vitamin D supplementation may be able to prevent the immune maladaptation and loss of tolerance that occur in preeclampsia, with evidence for an association obtained from various types of observational studies and clinical trials. There is also evidence from observational studies for potential long-term programming effects of vitamin D supplementation on immunological diseases (such as type 1 diabetes and allergic diseases), with evidence supporting the role of active vitamin D as a potent immunomodulator. This paper highlights the complex effects of active vitamin D on immunomodulation with long-term implications for the risk of immunological diseases. It is suggested that it is essential to avoid vitamin D deficiency during pregnancy, and while accumulating evidence suggests important benefits of further increases in the intake, further research is required to fully establish the influence of high dosages.

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