The Effect of Vitamin D Supplementation on Hepcidin, Iron Status, and Inflammation in Pregnant Women in the United Kingdom
Background and Objective
Iron and vitamin D deficiencies are common during pregnancy. Our aim was to identify whether antenatal vitamin D₃ supplementation affects iron status (via hepcidin suppression) and/or inflammation. Using a subset of the UK multicenter Maternal Vitamin D Osteoporosis Study (MAVIDOS)-a double-blinded, randomized, placebo-controlled trial (ISRCTN82927713; EudraCT2007-001716-23)-we performed a secondary laboratory analysis. Women with blood samples from early and late pregnancy (vitamin D₃ (1000 IU/day from ~14 weeks gestation n = 93; placebo n = 102) who gave birth in the springtime (March⁻May) were selected as we anticipated seeing the greatest treatment group difference in change in 25-hydroxyvitamin D (25OHD) concentration.
Outcomes were hepcidin, ferritin, C-reactive protein, and α1-acid glycoprotein concentration in late pregnancy (25OHD concentration was measured previously). By late pregnancy, 25OHD concentration increased by 17 nmol/L in the vitamin D₃ group and decreased by 11 nmol/L in the placebo group; hepcidin, ferritin, and inflammatory markers decreased but no treatment group differences were seen. In late pregnancy, positive relationships between 25OHD and hepcidin and 25OHD and ferritin in the placebo group were observed but not in the treatment group (group × 25OHD interaction, p < 0.02). Vitamin D₃ supplementation had no effect on hepcidin, ferritin, or inflammatory status suggesting no adjunctive value of vitamin D₃ in reducing rates of antenatal iron deficiency.
Venous blood samples were collected in early and late pregnancy into lithium heparin-coated tubes and the plasma were stored at −80 °C for subsequent analysis at MRC Elsie Widdowson Laboratory, Cambridge, UK. Hepcidin was measured by ELISA (Hepcidin 25 bioactive HS, DRG Diagnostics, Marburg, Germany; inter-assay % coefficient of variation (%CV) between 8–13) and ferritin, CRP, and AGP was measured on the automated platform by Dimension Xpand, Siemens (ferritin and high sensitivity-CRP kits from Siemens Healthcare, Erlangen, Germany, and AGP kits from Sentinel Diagnostics, Milano, Italy. Intra-assay %CV was <6 for ferritin and CRP and <11 for AGP). 25OHD had been measured as part of the main trial by radioimmunossay (Liaison, RIA automated platform, Diasorin, Stillwater, MN, USA) as previously described and was DEQAS accredited.