Circulating maternal concentrations of hormonally active
vitamin D [
calcitriol,
1,25(OH)(2)D] 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.