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Title: Daily cholecalciferol supplementation during pregnancy alters markers of regulatory immunity, inflammation, and clinical outcomes in a randomized controlled trial

Author
item Zerofsky, Melissa
item JACOBY, BRYON - Uc Davis Medical Center
item Pedersen, Theresa
item Stephensen, Charles

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/23/2016
Publication Date: N/A
Citation: N/A

Interpretive Summary: Vitamin D deficiency is common in pregnancy and may have adverse health effects for mothers and infants. For example, vitamin D deficiency may exacerbate the increase in blood pressure that normally occurs during pregnancy, and may also allow inappropriate activation of the immune system against fetal antigens, potentially causing a condition called preeclampsia. Vitamin D supplementation in pregnancy may thus decrease the risk of such adverse health effects. We assessed the effects of vitamin D supplementation during pregnancy on vitamin D status, blood pressure, markers of immune function and routine clinical outcomes by conducting a randomized, controlled, intervention of two doses of vitamin D (400 IU/d vs. 2,000 IU/d) from early in pregnancy through delivery in fifty-seven women at risk for vitamin D deficiency. Vitamin D status, immune function and clinical endpoints were assessed in mid- and late pregnancy. Supplementation with 2,000 IU vitamin D had a greater effect on vitamin D status than 400 IU. The percent of regulatory cells producing the cytokine interleukin-10, which can dampen potentially dangerous inflammation, increased significantly with the 2,000 IU treatment relative to the 400 IU control. The 2,000 IU treatment also tended to dampen the pregnancy-related increase in blood pressure, and tended to increase birthweight, but these differences were not statistically significant. In summary, 2,000 IU/d is more effective at increasing vitamin D status in pregnant women than 400 IU/d and is associated with increased regulatory immunity that may prevent adverse outcomes, such as preeclampsia, caused by excess inflammation.

Technical Abstract: Vitamin D deficiency is widespread in pregnancy and has been associated with adverse health conditions for mothers and infants. Vitamin D supplementation in pregnancy may support maintenance of pregnancy by its effects on adaptive and innate immunity. We assessed the effects of vitamin D supplementation during pregnancy on vitamin D status, regulatory and inflammatory T-cells, markers of innate immunity and systemic inflammation, and clinical outcomes including maternal blood pressure and birthweight. We conducted a randomized, controlled, double-blind intervention of two doses of vitamin D (400 IU/d vs. 2,000 IU/d) from <20 weeks through delivery in fifty-seven pregnant women at risk for vitamin D deficiency. Vitamin D status, immune function and clinical endpoints were assessed in mid- and late pregnancy. Supplementation with 2,000 IU vitamin D had a greater effect on vitamin D status than 400 IU. The percent of IL-10+ CD4+ regulatory cells increased significantly with the 2,000 IU treatment relative to the 400 IU control. FoxP3+ regulatory T-cells and inflammatory T-cells were not affected, nor were other immunologic endpoints. The 2,000 IU treatment tended to dampen the pregnancy-related increase in blood pressure, and tended to increase birthweight, but these differences were not statistically significant (p = 0.06). 2,000 IU/d is more effective at increasing vitamin D status in pregnant women than 400 IU/d and is associated with increased regulatory immunity that may prevent adverse outcomes, such as preeclampsia, caused by excess inflammation.