Antenatal Vitamin D3 Supplementation in Bangladesh: Randomized Controlled Trial (AViDD-2)

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

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.

Study Overview

• Status: Completed
• Conditions: Pregnancy
• Intervention / Treatment: Dietary supplement: Vitamin D3; Dietary supplement: Placebo control

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.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • International Centre for Diarrheal Disease Research, Bangladesh (icddr,b)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 34 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborators: International Centre for Diarrhoeal Disease Research, Bangladesh
• Investigators: Principal Investigator: Rubhana Raqib, PhD, International Centre for Diarrhoeal Disease Research, Bangladesh; Principal Investigator: Abdullah Baqui, MBBS, JHSPH; ICDDR,B; Principal Investigator: Daniel Roth, MD, Johns Hopkins Bloomberg School of Public Health

Publications and helpful links

General Publications

• Akhtar E, Mily A, Haq A, Al-Mahmud A, El-Arifeen S, Hel Baqui A, Roth DE, Raqib R. Prenatal high-dose vitamin D3 supplementation has balanced effects on cord blood Th1 and Th2 responses. Nutr J. 2016 Aug 9;15(1):75. doi: 10.1186/s12937-016-0194-5.
• Harrington J, Perumal N, Al Mahmud A, Baqui A, Roth DE. Vitamin D and fetal-neonatal calcium homeostasis: findings from a randomized controlled trial of high-dose antenatal vitamin D supplementation. Pediatr Res. 2014 Sep;76(3):302-9. doi: 10.1038/pr.2014.83. Epub 2014 Jun 17.
• Roth DE, Perumal N, Al Mahmud A, Baqui AH. Maternal vitamin D3 supplementation during the third trimester of pregnancy: effects on infant growth in a longitudinal follow-up study in Bangladesh. J Pediatr. 2013 Dec;163(6):1605-1611.e3. doi: 10.1016/j.jpeds.2013.07.030. Epub 2013 Aug 30.
• Roth DE, Al Mahmud A, Raqib R, Akhtar E, Perumal N, Pezzack B, Baqui AH. Randomized placebo-controlled trial of high-dose prenatal third-trimester vitamin D3 supplementation in Bangladesh: the AViDD trial. Nutr J. 2013 Apr 12;12:47. doi: 10.1186/1475-2891-12-47.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: May 18, 2010
• First Submitted That Met QC Criteria: May 18, 2010
• First Posted (Estimate): May 19, 2010

Study Record Updates

• Last Update Posted (Estimate): August 17, 2012
• Last Update Submitted That Met QC Criteria: August 16, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Vitamin D; Immunology; Micronutrients; Infant, Newborn; Infant, Newborn, Diseases; Developing countries; Bangladesh; cholecalciferol; Reproductive Health; cathelicidin; Perinatology; Maternal Nutrition Physiology
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: JHU-IRB2481; 02829-5 (Other Grant/Funding Number: Thrasher Research Fund)