Vitamin D supplementation during pregnancy: Effect on the neonatal immune system in a randomized controlled trial

Abstract

Background Programming of the immune system during fetal development can influence asthma-related risk factors and outcomes in later life. Vitamin D is a well-recognized immune modulator, and deficiency of this nutrient during pregnancy is hypothesized to influence disease development in offspring. Objective We sought to investigate the effect on neonatal immunity of maternal supplementation with 4400 IU/d vitamin D3 during the second and third trimesters of pregnancy by using a subset of cord blood samples from a randomized, double-blind, placebo-controlled clinical trial (the Vitamin D Antenatal Asthma Reduction Trial). Methods Cord blood samples from neonates born to mothers supplemented with 4400 IU/d (n = 26) or 400 IU/d (n = 25) of vitamin D3 were analyzed for immune cell composition by flow cytometry, Toll-like receptor (TLR) expression by quantitative PCR, and cytokine secretion after stimulation with mitogenic, TLR, and T-cell stimuli by cytometric bead array. Responsiveness to the glucocorticoid dexamethasone was determined. Results Supplementation of mothers with 4400 IU of vitamin D3 resulted in an enhanced broad-spectrum proinflammatory cytokine response of cord blood mononuclear cells to innate and mitogenic stimuli (P =.0009), with an average 1.7- to 2.1-fold increase in levels of several proinflammatory cytokines (GM-CSF, IFN-γ IL-1β IL-6, and IL-8) across stimuli, a higher gene expression level of TLR2 (P =.02) and TLR9 (P =.02), a greater than 4-fold increase in IL-17A (P =.03) production after polyclonal T-cell stimulation, and an enhanced IL-10 response of cord blood mononuclear cells to dexamethasone treatment in culture (P =.018). Conclusion Vitamin D exposure during fetal development influences the immune system of the neonate, which can contribute to protection from asthma-related, including infectious, outcomes in early life.