Effect of Maternal Vitamin D3 Supplementation on Iron Status During Pregnancy and Early Infancy
Condition: Pregnancy
Study type: Interventional
Phase: Phase 3

Summary: 
      This is a secondary-use study based on previously-collected data and blood samples from a
      previously completed double-blind, dose-ranging trial of maternal prenatal and postpartum
      vitamin D supplementation in Dhaka, Bangladesh (NCT01924013). The aim of this sub-study is to
      examine the effect of vitamin D supplementation on iron status during pregnancy and early
      infancy.
    

Detailed description: 
      The risk of both low iron and vitamin D status have been recognized as public health concerns
      among pregnant women and young children, with high rates of deficiency in low-and
      middle-income countries. Through its involvement in regulation of the hepcidin-ferroportin
      axis, as well as its potential to increase the expression of the erythropoietin receptor,
      vitamin D has been suggested as a modulator of iron homeostasis. Vitamin D supplementation
      may therefore represent a candidate facilitator for the management of iron deficiency, yet
      few intervention trials have directly assessed the effect of vitamin D supplementation on
      biomarkers of iron status.

      To examine the effect of vitamin D supplementation on iron status during pregnancy and early
      infancy, data and blood samples will be drawn from a completed double-blind, dose-ranging
      trial of maternal prenatal and postpartum vitamin D supplementation. Women at 17-24 weeks'
      gestation were randomized to 1 of 5 dose groups comprising a prenatal; postpartum regimen of
      placebo; placebo, 4200;0, 16800;0, 28000;0 or 28000;28000 IU vitamin D3/week until 26 weeks
      postpartum. Enrolment (n=1300) was completed in September 2015, and all infants were
      delivered by February 2016. The MDIG trial was primarily designed to determine the effect of
      maternal vitamin D on infant length at 12 months of age (with follow-up continuing until
      infants reached 24 months of age; completed in March 2018).

      Analyses of serum ferritin and related iron biomarkers (serum iron, transferrin, soluble
      transferrin receptor, hepcidin), and inflammatory makers (e.g. CRP), will be conducted using
      previously collected stored blood samples. Linear regression models will be used to assess
      the effect of vitamin D supplementation on the biomarkers of interest among pregnant women
      and their infants at 6 months of age.

      To examine the potential dose-response relation between prenatal vitamin D treatment dose
      (i.e., across all 4 assigned prenatal vitamin D doses by combining the 2 high-dose prenatal
      vitamin D treatment groups) and the biomarker of interest, linear regression models will be
      fitted using the assigned prenatal vitamin D treatment group as the categorical exposure
      variable and the specified biomarker as the (continuous) outcome variable. Data will be
      reported as mean differences (or mean % differences, if applicable) and 95% CIs.

      To explore potential effects of prenatal only versus prenatal plus postpartum vitamin D
      supplementation on Hb and ferritin concentrations among infants at 6 months of age, a similar
      dose-response analysis will be conducted across all 5 treatment groups (i.e., disaggregation
      of the 2 high-dose prenatal vitamin D groups), for which the investigators will regress the
      biomarker (Hb as a continuous variable) on the vitamin D treatment group assigned during the
      prenatal and postpartum periods (as a categorical variable). Differences in each
      supplementation group will therefore be compared to the placebo group, and expressed as mean
      differences (or geometric means, or mean % differences, if applicable) and 95% CIs.

      Given the influence of inflammation on serum ferritin concentrations, secondary analyses will
      include inflammatory markers (e.g. CRP) as covariates to test the role of inflammation in
      mediating the association between the vitamin D intervention and serum ferritin
      concentrations.
    

Intervention name(s): Placebo; Vitamin D3 (cholecalciferol)
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): This product is identical in appearance, taste and texture to the experimental formulation but does not include any vitamin D3.; The intervention is an oral tablet containing vitamin D3 (cholecalciferol). Each weekly dose consists of a single tablet. Vitamin D3 content of the dose depends on the intervention group.
Intervention MeSH terms: Vitamin D; Cholecalciferol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Maternal Nutrition; Vitamin D; Iron Status; Iron Deficiency