Antenatal Vitamin D3 Supplementation in Bangladesh: Randomized Controlled Trial

Study Overview
=================
Brief Summary
-----------------
This study is a randomized placebo-controlled trial of oral weekly vitamin D3 (cholecalciferol) supplementation during the third trimester of pregnancy among women in Dhaka, Bangladesh. The overall goal of the study is to establish whether there is evidence that improving vitamin D status among pregnant women in Bangladesh will enhance the resistance of the infant offspring to infection. The aims of the study are to assess the effect of supplementation on 1) maternal and infant vitamin D status (based on blood concentrations of a vitamin D metabolite) and, 2) markers of neonatal immune function.

Detailed Description
-----------------
The primary aims of this study are: AIM #1 - To assess the effect of weekly antenatal administration of oral vitamin D3 (875 mcg/week = 35,000 IU week ≈ 5,000 IU per day) started in the third trimester (26-29 weeks gestation) on maternal vitamin D status and fetal-neonatal vitamin D status (cord blood), in comparison to a placebo control supplement. AIM #2 - To demonstrate the maternal and fetal safety of weekly maternal antenatal (second and third-trimester) vitamin D supplementation at a dose of 875 mcg/week by monitoring maternal serum calcium, urinary calcium excretion, cord blood calcium concentration, and newborn clinical parameters. AIM #3 - To measure the effect of antenatal vitamin D supplementation on selected biomarkers of fetal-neonatal immune function in cord blood: in vitro stimulated cord blood mononuclear cell (CBMC) LL-37 expression, gene expression related to inflammatory and immunoregulatory pathways, Th1/Th2 cytokine secretion, and bactericidal properties.

Official Title
-----------------
The Effect of Antenatal Vitamin D Supplementation on Maternal-fetal Vitamin D Status and Neonatal Immune Function: a Randomized Controlled Trial in Bangladesh

Conditions
-----------------
Pregnancy

Intervention / Treatment
-----------------
* Dietary Supplement: Vitamin D3
* Dietary Supplement: Placebo control


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women aged 18 to <35 years. Current residence in Dhaka at a fixed address Plans to have the delivery performed at the Shimantik maternity center, and to stay in Dhaka throughout the pregnancy and for at least one month past the date of delivery. Gestational age of 26th to 29th (inclusive), estimated based on the first day of the last menstrual period (LMP). Exclusion Criteria: Use of any dietary supplement containing more than 400 IU/day (10 mcg/day) of vitamin D within the month prior to enrolment, or refusal to stop taking supplemental vitamin D at any dose after enrollment. Current use of anti-convulsant or anti-mycobacterial (tuberculosis) medications. Severe anemia (hemoglobin concentration < 70 g/L). Complicated medical or obstetric history that may increase the risk of preterm birth or labor/delivery complications, based on self-report or clinical assessment by physician (e.g., cardiovascular disease, uterine hemorrhage, placenta previa, threatened abortion, hypertension, preeclampsia, preterm labor, or multiple gestation). Prior history of delivery of an infant with a major congenital anomaly, birth asphyxia, or perinatal death (stillbirth or death within first week of life).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 34 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D3<br>Vitamin D3 (cholecalciferol) | Dietary Supplement: Vitamin D3<br>* 35,000 IU per week, started at 26-29 weeks gestation, until delivery.<br>* Other names: Cholecalciferol; Vigantol Oil;|
| Placebo Comparator: Control<br>Placebo control group | Dietary Supplement: Placebo control<br>* Miglyol 812, administered weekly from 26-29 weeks gestation until delivery.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum 25-hydroxyvitamin D concentration | Biomarker of vitamin D status. | Maternal: during 3rd trimester; Neonatal (cord blood) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum calcium concentration |  | Maternal:3rd trimester; Cord blood. | 
| Urine Ca:Cr ration |  | Maternal- 3rd trimester | 
| Neonatal immune function | Selected markers of innate and adaptive immunity. | Cord blood | 
| Infant growth | Infant growth parameters during postnatal follow-up, up to 12 months of age | Postnatal observational follow-up phase | 
| Infant and maternal postnatal vitamin D status |  | Postnatal observational follow-up phase | 
| Neonatal serum calcium | Infant serum calcium during the first week postnatal. | 1st week postnatal | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vitamin D, cholecalciferol, Micronutrients, Developing countries, Bangladesh, Infant, Newborn, Reproductive Health, Infant, Newborn, Diseases, Perinatology, Immunology, cathelicidin, Maternal Nutrition Physiology