Clinical trial NCT01126528: Antenatal Vitamin D3 Supplementation in Bangladesh: Randomized Controlled Trial
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pregnancy
Keywords: Vitamin D
cholecalciferol
Micronutrients
Developing countries
Bangladesh
Infant, Newborn
Reproductive Health
Infant, Newborn, Diseases
Perinatology
Immunology
cathelicidin
Maternal Nutrition Physiology
Lead sponsor: Johns Hopkins Bloomberg School of Public Health
Sponsor class: OTHER
Collaborators: name: International Centre for Diarrhoeal Disease Research, Bangladesh
First posted: 2010-05-19
Enrollment: 160
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 34
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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).

Primary outcomes:
measure: Serum 25-hydroxyvitamin D concentration
timeFrame: Maternal: during 3rd trimester; Neonatal (cord blood)
Secondary outcomes:
measure: Serum calcium concentration
timeFrame: Maternal:3rd trimester; Cord blood.
measure: Urine Ca:Cr ration
timeFrame: Maternal- 3rd trimester
measure: Neonatal immune function
timeFrame: Cord blood
measure: Infant growth
timeFrame: Postnatal observational follow-up phase
measure: Infant and maternal postnatal vitamin D status
timeFrame: Postnatal observational follow-up phase
measure: Neonatal serum calcium
timeFrame: 1st week postnatal
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B)
Study officials:
affiliation: JHSPH; ICDDR,B
name: Abdullah Baqui, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins Bloomberg School of Public Health
name: Daniel Roth, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Rubhana Raqib, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.