Vitamin B12 Supplementation to Improve B12 Status and Child Development

Effects of Vitamin B12 Fortified Milk Supplementation During Pregnancy and 6 Month Postpartum to Improve B12 Status and Child Development

Impaired vitamin B12 (B12) status during pregnancy is associated with increased risk of birth defects and common complications (e.g. intrauterine growth restriction, neural tube defects), and possibly immune function impairment. The newborns and infants of B12-deficient mothers have low B12 stores at birth, further exacerbated by a very low concentration of B12 in breast milk that may hinder their growth and development. In regions such as Bangladesh, many women of reproductive age have inadequate B12 status, probably due to low intake of animal source food. Vitamin B12 intake and status in pregnancy and lactation is potentially insufficient to prevent impaired child development and immune function related to inadequate B12 status. The investigators hypothesize that prolonged vitamin B12 supplementation through fortified milk starting from early pregnancy up to 6 mo-postpartum will improve: (1) biomarkers of vitamin B12 status in mothers-infant pairs (2) vaccine specific adaptive immunity in infants; (3) neurological and cognitive function in infants.

Study Overview

• Status: Completed
• Conditions: Early Pregnancy
• Intervention / Treatment: Dietary supplement: Vitamin B12 fortified UHT milk; Dietary supplement: Plain UHT milk

Detailed Description

The investigators aim to conduct a double-blind, randomized trial, to investigate the effects of B12-fortified milk on maternal and infant B12 status, immune function and child development. Pregnant women (n=148) will be randomized to receive B12-fortified milk (100 μg/day) or milk without fortification. The daily supplementation beginning at the baseline visit (GW 11-14) will continue until 6 mo-postpartum. Biomarkers of B12 status will be measured in mothers (GW 11-14 and 6-mo postpartum) and infants (3 and 6-mo). Infant development (6 and 12-mo) will be evaluated by Bayley Scales of Infant and Toddler Development. Immune responses will be measured in infant at 3 and 6-mo. Data on socioeconomic status, dietary diversity, and anthropometric indices will be recorded at baseline. Additional tests in mothers include screening for H. pylori and plasma gastrin.

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh, 1205
    • Maternal and Child Health Training Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 - 35 y old 2. 11-14 wk pregnant (based on last menstrual period) 3. Willing to stay in Dhaka during pregnancy and remain in the area for the 12 mo following recruitment 4. Willing to be admitted in the clinic for delivery 5. Intends to exclusively or predominantly breastfeed infant until 6 mo of age

-

Exclusion Criteria:

1. Women with severe anemia; Hb concentration <70 g/L 2. History or presence of systemic disease such as Diabetes mellitus, Hypertension 3. History of previous complicated pregnancies, pre-term delivery, or abortion 4. Current use of supplements containing vitamin B12 5. Children with acute illness or features suggestive of any chronic disease such as tuberculosis, any congenital anomalies such as cleft lip or palate.

-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vitamin B12-fortified UHT milk; Supplementation group (N=74) that will receive vitamin B12 fortified UHT milk daily	Dietary supplement: Vitamin B12 fortified UHT milk; Daily intake of 200 mL of UHT milk fortified with 100 µg vitamin B12
Placebo Comparator: Plain UHT milk; Placebo group (N=74) that will receive plain UHT milk daily	Dietary supplement: Plain UHT milk; Daily intake of 200 mL of plain UHT milk

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in concentrations of biomarkers of vitamin B12 in mother-child pairs	The investigators will determine the change in concentrations of biomarkers of B12 ( based on measurement of B12, MMA, tHcy, holoTC, cB12, folate in plasma; B12 in breast milk)	Baseline and 6 months postpartum
Vaccine specific immunity in infants	The investigators will determine the concentrations of vaccine specific IgA and IgG in plasma	6 months
Cognitive, Language and Motor Composite Score	The outcomes are measured by Bayley-III test	12 months
Nuroinflammatory cytokines	The investigators will determine the change in concentrations of EGF and TNF-α in plasma	12 months

Collaborators and Investigators

• Sponsor: International Centre for Diarrhoeal Disease Research, Bangladesh
• Collaborators: University of California, Davis; Nestlé Foundation
• Investigators: Principal Investigator: Towfida J Siddiqua, PhD, International Centre for Diarrhoeal Disease Research, Bangladesh

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2017
• Primary Completion (Actual): October 30, 2021
• Study Completion (Actual): October 30, 2021

Study Registration Dates

• First Submitted: August 13, 2017
• First Submitted That Met QC Criteria: August 20, 2017
• First Posted (Actual): August 23, 2017

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 15, 2023
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Vitamin B12, Fortified milk, Immunity, Child development
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Vitamin B 12; Hydroxocobalamin
• Other Study ID Numbers: PR-16003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No