Maternal and Cord Blood 25-Hydroxyvitamin D Are Associated with Increased Cord Blood and Naive and Activated Regulatory T Cells: The Barwon Infant Study.

Vitamin D has shown immune-modulatory effects but mostly in in vitro and animal studies. Regulatory T cells (Treg) are important for a balanced immune system. The relationship between vitamin D on the number of circulating neonatal Treg is unclear. We sought to investigate the association between maternal and neonatal vitamin D metabolites and cord blood (CB) Treg subsets. In a cohort of Australian infants ( = 1074), recruited using an unselected antenatal sampling frame, 158 mother-infant pairs had data on the following: 1) 25-hydroxyvitamin D (25(OH)D) measures in both maternal peripheral blood (28- to 32-wk gestation) and infant CB; 2) proportions (percentage of CD4 T cells) of CB Treg subsets (CD4CD45RA FOXP3 naive Treg, and CD4CD45RA FOXP3 activated Treg [aTreg]); and 3) possible confounders, including maternal personal UV radiation. Multiple regression analyses were used. The median 25(OH)D was 85.4 and 50.7 nmol/l for maternal and CB samples, respectively. Higher maternal 25(OH)D levels were associated with increased CB naive Treg (relative adjusted mean difference [AMD] per 25 nmol/l increase: 5%; 95% confidence interval [CI]: 1-9%), and aTreg (AMD per 25 nmol/l increase: 17%; 95% CI: 6-28%). Furthermore, a positive association between CB 25(OH)D levels and CB aTreg (AMD per 25 nmol/l increase: 29%; 95% CI: 13-48%) was also evident. These results persisted after adjustment for other factors such as maternal personal UV radiation and season of birth. 25(OH)D may play a role in the adaptive neonatal immune system via induction of FOXP3 Tregs. Further studies of immune priming actions of antenatal 25(OH)D are warranted.