Clinical trial NCT04764955: Effect of Maternal Vitamin D3 Supplementation on Iron Status During Pregnancy and Early Infancy
Official title: Effect of Maternal Vitamin D3 Supplementation on Iron Status During Pregnancy and Early Infancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pregnancy
Keywords: Maternal Nutrition
Vitamin D
Iron Status
Iron Deficiency
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Bill and Melinda Gates Foundation
name: King's College London
First posted: 2021-02-21
Enrollment: 1300
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Women aged 18 years and above.
* Gestational age of 17 to 24 completed weeks estimated based on recalled last menstrual period (LMP) and/or ultrasound.
* Intends to permanently reside in the trial catchment area for at least 18 months
* MDIG trial participants with availability of at least one measurement of the biomarkers of interest (serum ferritin, circulating hepcidin, transferrin, soluble transferrin receptor, serum iron and/or whole-blood Hb).

Exclusion Criteria:

* History of medical conditions that may predispose the participant to vitamin D sensitivity, altered vitamin D metabolism and/or hypercalcemia, or history of renal calculi.
* High-risk pregnancy based on one or more of the following findings by point-of-care testing:
* - Severe anemia: hemoglobin \<70 g/L assessed by Hemocue.
* - Moderate-severe proteinuria: ≥ 300 mg/dl (3+ or 4+) based on urine dipstick.
* - Hypertension: systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg.
* - Multiple gestation, major congenital anomaly, or severe oligohydramnios based on maternal history and/or ultrasound.
* - Unwillingness to stop taking non-study vitamin D or calcium supplements or a multivitamin with calcium and/or vitamin D.
* - Currently prescribed vitamin D supplements as part of a physician's treatment plan for vitamin D deficiency.
* - Previous participation in the same study.

Primary outcomes:
measure: Maternal serum ferritin concentration at delivery
timeFrame: Delivery
Secondary outcomes:
measure: Maternal transferrin saturation at delivery
timeFrame: Delivery
measure: Maternal soluble transferrin receptor at delivery
timeFrame: Delivery
measure: Maternal circulating hepcidin at delivery
timeFrame: Delivery
measure: Infant whole-blood Hb concentration
timeFrame: 6 months of age
measure: Infant ferritin concentration
timeFrame: 6 months of age
measure: Maternal total iron binding capacity at delivery
timeFrame: Delivery
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: International Centre for Diarrhoeal Disease Research, Bangladesh
Study officials:
affiliation: The Hospital for Sick Children
name: Daniel E Roth, MD
role: PRINCIPAL_INVESTIGATOR
References: